Showing papers by "Tetsu Tanaka published in 2021"

Leaflet Configuration and Residual Tricuspid Regurgitation After Transcatheter Edge-to-Edge Tricuspid Repair

Abstract: Objectives This study aimed to assess the anatomical leaflet variation and investigate its impact on the procedural outcome in patients undergoing transcatheter edge-to-edge tricuspid repair. Background Tricuspid regurgitation (TR) is associated with a poor prognosis. Methods The study participants were consecutive patients who underwent transcatheter edge-to-edge tricuspid repair with the MitraClip, TriClip, or PASCAL systems from June 2015 to July 2020 at the Bonn Heart Center. The tricuspid leaflet morphologies were imaged using 2-dimensional and 3-dimensional transesophageal echocardiography. The severity of TR was assessed according to the 5-grade scheme. The primary endpoint was residual TR ≥3+ within 30 days. Results Of the 145 study participants, 103 (71.1%) participants were categorized as the 3-leaflet configuration, while 42 (28.9%) were categorized as the 4-leaflet configuration. Successful device implantation was achieved in 136 (93.8%) patients, with no statistical difference between the 3-leaflet and 4-leaflet configuration groups. However, compared with patients with a 3-leaflet configuration, patients with 4-leaflet configuration more frequently had residual TR ≥3+ (18.4% vs 38.1%; P = 0.018). In the multivariable model, the 4-leaflet configuration was associated with an increased risk of residual TR ≥3+ (odds ratio: 2.65; 95% CI 1.15-6.10; P = 0.022), independent of baseline TR grade, coaptation gap width, and TR jet location. After 1-year follow-up, compared with patients with residual TR Conclusions A 4-leaflet configuration of the tricuspid valve is observed in approximately one-third of patients undergoing transcatheter edge-to-edge tricuspid repair, which is associated with an increased risk of residual TR after the procedure.

Prognostic impact of hepatorenal function in patients undergoing transcatheter tricuspid valve repair.

Abstract: Hepatorenal dysfunction is a strong risk factor in patients with heart failure (HF). We investigated the prognostic significance of hepatorenal dysfunction in 172 consecutive patients undergoing transcatheter tricuspid valve repair (TTVR). The model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln(serum total bilirubin [mg/dl]) + 11.76 × ln(serum creatinine [mg/dl]) + 9.44. Patients were stratified into two groups: high (≥ 14) or low (< 14) MELD-XI score, according to the best cut-off value to predict a one-year composite outcome consisting of all-cause mortality and HF hospitalization. Compared to patients with low MELD-XI score (n = 121), patients with high MELD-XI score (n = 51) had a higher incidence of the composite outcome (47.1% vs. 17.4%; p < 0.0001). In the multivariable analysis, the MELD-XI score was an independent predictor of the composite outcome (adjusted hazard ratio: 1.12; 95% confidence interval [CI] 1.05–1.19; p = 0.0003). In addition, post-procedural TR < 3 + after TTVR was independently associated with a reduction in MELD-XI score six months after TTVR (adjusted odds ratio: 3.37; 95% CI 1.09–10.40; p = 0.03). Thus, the MELD-XI score was associated with the risk of one-year composite outcome, consisting of mortality and HF hospitalization, after TTVR and may help the risk stratification in patients undergoing TTVR.

Development of Manganese Nitride Resistor with Near-Zero Temperature-Coefficient of Resistance to Achieve High-Thermal-Stability ICs

Abstract: The resistance of the metal wirings in the integrated circuits increases due to the decrease of the mean free path of electrons with the temperature increase. This thermal instability requires redundancy circuits. On the other hand, several materials have the saturation characteristics of the mean free path around room temperature. The anti-perovskite manganese nitride compound material is one of them. The anti-perovskite manganese nitride compounds show a flat resistance-temperature curve around room temperature. However, the flat resistance-temperature curves have been obtained with only the sintered bulk materials. It has not become clear the characteristics of the manganese nitride compounds in the micro/nanoscale. In this study, we proposed manganese nitride wiring for high-thermal-stability systems. Then, we fabricated and evaluated the micro/nanoscale manganese nitride compound wiring with the complementary metal-oxide-semiconductor compatible process.

Prognostic significance of the get with the guidelines-heart failure (GWTG-HF) risk score in patients undergoing trans-catheter tricuspid valve repair (TTVR)

Abstract: The Get-With-The-Guidelines-Heart-Failure (GWTG-HF) score is a risk assessment tool to predict mortality in patients with heart-failure (HF). We aimed to evaluate the GWTG-HF score for risk stratification in HF patients with tricuspid regurgitation undergoing trans-catheter tricuspid valve repair (TTVR). In total, 181 patients who underwent TTVR via edge-to-edge repair (86%) or annuloplasty (14%) were enrolled. Patients were categorized into a low- (≤ 43 points), intermediate- (44–53 points) and high-risk score groups (≥ 54 points). TTVR led to an improvement of TR (p < 0.0001) and NYHA (p < 0.0001). Kaplan–Meier analysis and log-rank test revealed that higher GWTG-HF scores were associated with reduced rates of event-free survival regarding mortality (96% vs 89% vs 73%, respectively, p = 0.001) and hospitalization for heart failure (HHF) (89% vs 86% vs 74%, respectively, p = 0.026). After adjusting for important variables like renal function, left ventricular ejection fraction and mitral regurgitation, the GWTG-HF score remained an independent predictor of the composite endpoint of HHF or mortality (hazard ratio 1.04 per 1-point increase, p = 0.029). Other remaining predictors were renal function and mitral regurgitation. The GWTG-HF score used as a risk stratification tool of mortality and HHF maintains its prognostic value in a HF population with severe TR undergoing TTVR.

FOWLP-Based Flexible Hybrid Electronics with 3D-IC Chiplets for Smart Skin Display

Abstract: This paper deals with a flexible 3D-IC system fabrication methodology. Mini-LEDs and 3D-IC chiplets divided from a large 3D-IC with Cu-TSVs are embedded in an elastomer PDMS based on die-first FOWLP for heterogeneously integrating them into Smart Skin Display as a biomedical/wearable FHE (flexible hybrid electronics). We address a serious die-shift issue for the tiny chips in die-first FOWLP by using a new anchoring layer technique to drastically reduce the shift within $2.7\ \mu\mathrm{m}$ including assembly positioning errors. The mechanical/electrical properties of the flexible array of 3D-IC chiplets are characterized before and after repeated bending with a curvature radius of 10 mm. In addition, stress neutral axes are designed to stably endure bending cycle applicable to the biomedical/wearable FHE with multi-level metallization.

Early response of right-ventricular function to percutaneous mitral valve repair.

Abstract: BACKGROUND The change in right-ventricular function (RVF) after transcatheter mitral valve repair is still poorly understood. We assessed the early response of RVF to the MitraClip procedure and its clinical relevance. METHODS We analyzed consecutive patients who underwent a MitraClip procedure to treat MR between August 2010 and March 2019 in the Heart Failure Network Rhineland registry. RVF was assessed before and after the procedure. Impaired RVF was defined as an RV fractional area change (RVFAC) < 35% or tricuspid annular plane systolic excursion (TAPSE) < 16 mm. RESULTS 816 eligible patients (77 ± 9 years, 58.5% male) were included in the analysis. Baseline values of RVF were: RVFAC 38.6 (IQR 29.7-46.7) % and TAPSE 17.0 (IQR 14.0-21.0) mm. At a median time of 3 (IQR 2-5) days after the procedure, the RVF remained normal in 34% (n = 274), normalized in 17% (n = 140), deteriorated in 15% (n = 125), and was persistently impaired in 34% (n = 277) of patients. The RVF response was significantly associated with a composite outcome of all-cause mortality and hospitalization due to heart failure within a 2-year follow-up. Compared to stable/normal RVF, the adjusted hazard ratios for the outcome were 1.78 (95% CI 1.10-2.86) for normalized RVF, 1.89 (95% CI 1.34-3.15) for deteriorated RVF, and 2.25 (95% CI 1.47-3.44) for persistently impaired RVF. Changes in TAPSE and RVFAC as continuous variables were significantly correlated with the outcome. CONCLUSION An early change in RVF following transcatheter mitral valve repair is predictive of mortality and hospitalization due to heart failure during follow-up. Early response of RVF after MitraClip and its clinical significance. An acute, early change in RVF can be observed following the MitraClip procedure, which is associated with the risk of mortality and hospitalization for HF.

Multimodal Functional Analysis Platform: 1. Ultrathin Fluorescence Endoscope Imaging System Enables Flexible Functional Brain Imaging.

Abstract: To elucidate the expression mechanisms of brain functions, we have developed an ultrathin fluorescence endoscope imaging system (U-FEIS) that can image cells in the brain at any depth while minimizing the invasion. The endoscope part of U-FEIS consists of a GRIN lens and a 10,000-pixel image fiber with a diameter of 450 μm. The specialized microscope of U-FEIS is within 30 cm square and includes lenses and optical filters optimized for the endoscope. Using U-FEIS, we successfully visualized neurons expressing GFP with single-cell resolution and recorded the multineuronal activities in vitro and in vivo. U-FEIS can also perform imaging and optical stimulation simultaneously. Therefore, U-FEIS should be a powerful optical tool in neuroscience research.

Prognostic value of hepatorenal function following transcatheter edge-to-edge mitral valve repair

Abstract: Hepatorenal dysfunction is a strong prognostic predictor in patients with heart failure. However, the prognostic impact of the hepatorenal dysfunction in patients undergoing transcatheter mitral valve repair (TMVR) has not been well studied. In consecutive patients who underwent edge-to-edge TMVR at three German centers, the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln [serum total bilirubin (mg/dl)] + 11.76 × ln [serum creatinine (mg/dl)] + 9.44. Patients were stratified into high (> 11) or low (≤ 11) MELD-XI score of which an incidence of the composite outcome, consisting of all-cause mortality and heart failure hospitalization, within 2 years after TMVR was assessed. Of the 881 patients, the mean MELD-XI score was 11.0 ± 5.9, and 415 patients (47.1%) had high MELD-XI score. The MELD-XI score was correlated with male, effective regurgitant orifice area, and tricuspid regurgitation severity and inversely related to left ventricular ejection fraction. Patients with high MELD-XI score had a higher incidence of the composite outcome than those with low MELD-XI score (47.7% vs. 29.8%; p < 0.0001), and in multivariable analysis, the high MELD-XI score was an independent predictor of the composite outcome [adjusted hazard ratio (HR) 1.34; 95% confidence interval (CI) 1.02–1.77; p = 0.04). Additionally, the MELD-XI score as a continuous variable was also an independent predictor (adjusted HR 1.02; 95% CI 1.00–1.05; p = 0.048). The MELD-XI score was associated with clinical outcomes within 2 years after TMVR and can be a useful risk-stratification tool in patients undergoing TMVR.

Periprocedural changes in natriuretic peptide levels and clinical outcome after transcatheter mitral valve repair.

Abstract: AIMS This multicentre study investigated the association of periprocedural changes in the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with clinical outcomes after transcatheter edge-to-edge mitral valve repair (TMVR). METHODS AND RESULTS Patients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT-proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT-proBNP following TMVR were assessed as the percent change in NT-proBNP between baseline and the 2 month follow-up, and the significant reduction in NT-proBNP was defined as a decrease of >30% in the follow-up NT-proBNP compared with the pre-procedural NT-proBNP level. Primary outcome was defined as a composite outcome consisting of all-cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut-off value of pre-procedural NT-proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut-off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT-proBNP (>30%) following the procedure. Patients with the NT-proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT-proBNP (31.4% vs. 40.2%; log-rank P = 0.03). The significant reduction in NT-proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45-0.97; P = 0.04], independently of pre-procedural NT-proBNP levels and other clinical parameters. The percent change in NT-proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94-0.98; P 2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03-2.17; P = 0.03); however, patients with a higher pre-procedural NT-proBNP who achieved the significant reduction in NT-proBNP had a similar risk of the composite outcome to those with a lower pre-procedural NT-proBNP. CONCLUSIONS Changes in sequential NT-proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT-proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post-procedural management after TMVR.

Wafer-Level Flexible 3D Corrugated Interconnect Formation for Scalable In-Mold Electronics with Embedded Chiplets

Abstract: We have reported a new flexible hybrid electronics (FHE) whose structure is consisting of heterogeneous small/thin/rigid chiplets embedded in 2D molded polymeric substrates such as PDMS and hydrogel on which fine-pitch fanout RDLs are formed by die-first or RDL-first FOWLP. In this study, we apply this FHE methodology to flexible 3D In-Mold Electronics (IME) for highly integrated 3D electronics. 1-mm-square Si chiplets are embedded in PDMS and biocompatible Au RDLs are formed on the elastomer in die-first FOWLP processing, and finally, the resulting 2D FHE (2D-PDMS) is re-molded again to give contact lens-shaped flexible 3D IME (3D-PDMS). In addition, we design the flexible 3D interconnections with self-assembled corrugation of out-of-plane tortuousness by controlling a CTE mismatch between the Au layer and the underneath insulator of flexible epoxy formed on the PDMS.

Multimodal Functional Analysis Platform: 3. Spherical Treadmill System for Small Animals.

Abstract: In the application of advanced neuroscience techniques including optogenetics to small awake animals, it is often necessary to restrict the animal’s movements. A spherical treadmill is a beneficial option that enables virtual locomotion of body- or head-restrained small animals. Besides, it has a wide application range, including virtual reality experiments. This chapter describes the fundamentals of a spherical treadmill for researchers who want to start experiments with it. First, we describe the physical aspect of a spherical treadmill based on the simple mechanical analysis. Next, we explain the basics of data logging and preprocessing for behavioral analysis. We also provide simple computer programs that work for the purpose.

Multimodal Functional Analysis Platform: 2. Development of Si Opto-Electro Multifunctional Neural Probe with Multiple Optical Waveguides and Embedded Optical Fiber for Optogenetics.

Abstract: We have developed a Si opt-electro multifunctional neural probe with multiple waveguides and embedded optical fiber for highly accurate optical stimulation. The Si opt-electro multifunctional neural probe had 16 recording sites, three optical waveguides, and metal cover for suppressing light leakage. The other opt-electro multifunctional neural probe had an optical fiber in the trench of the probe shank, which leads to fewer damages to tissues. We evaluated the electrochemical properties of the recording sites and confirmed that the neural probe had suitable characteristics for neural recording. We also demonstrated the optical stimulation to the neurons expressing ChR2 using our probe. As a result, we succeeded in multisite optical stimulation and observed that no light leakage from the optical waveguides because of the metal cover. From in vivo experiments, we successfully recorded optically modulated local field potential using the fabricated Si neural probe with optical waveguides. Moreover, we applied current source density analysis to the recorded LFPs. As a result, we confirmed that the light-induced membrane current sinks in the locally stimulated area. The Si opto-electro multifunctional neural probe is one of the most versatile tools for optogenetics.

Possible Neoangiogenesis in Achilles Tendon Xanthoma with Familial Hypercholesterolemia: A Novel Approach to Achilles Tendon Xanthoma.

Abstract: Achilles tendon xanthoma (ATX) is one of the typical features of familial hypercholesterolemia (FH). The morphological evaluation of ATX by X-ray radiography is widely recognized; however, the utility of other imaging modalities remains unclear. We herein report two cases of FH in which Doppler ultrasound imaging demonstrated a microvascular flow in ATX that only rarely could be observed in normal Achilles tendons. Neoangiogenesis accompanies chronic inflammation and it may play an important role in the deposition of cholesterol crystals leading to ATX. In addition to the morphological evaluation of ATX, the assessment of neoangiogenesis may therefore be essential for the evaluation of ATX.

Multimodal Functional Analysis Platform: 4. Optogenetics-Induced Oscillatory Activation to Explore Neural Circuits.

Abstract: To elucidate neural mechanisms underlying oscillatory phenomena in brain function, we have developed optogenetic tools and statistical methods. Specifically, opto-current-clamp induced oscillation reveals intrinsic frequency preferences in the neural circuits by oscillatory resonance. Furthermore, resonance or entrainment to intrinsic frequency is state-dependent. When resonance phenomena go beyond a certain range, it could even induce epileptic seizure in highly reproducible manner. We are able to study how seizures start, develop, and stop in neural circuits. Therefore, the optogenetics-induced oscillatory activation is a powerful tool in neuroscience research