Publications by authors named "Saki Ito"

31 Publications

Final 3-year clinical outcomes following transcatheter aortic valve implantation with a supra-annular self-expanding repositionable valve in a real-world setting: Results from the multicenter FORWARD study.

Catheter Cardiovasc Interv 2021 Jul 31. Epub 2021 Jul 31.

Department of Medicine, University of Bonn, Bonn, Germany.

Objectives: The Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3-year clinical follow up of the FORWARD study.

Background: Transcatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long-term clinical outcome data with the Evolut R platform are scarce.

Methods: FORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart-Team assessment. TAVR was attempted in 1039 patients.

Results: Mean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all-cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all-cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all-cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low.

Conclusions: The Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve-related adverse events were low.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.29889DOI Listing
July 2021

Electrocardiogram screening for aortic valve stenosis using artificial intelligence.

Eur Heart J 2021 08;42(30):2885-2896

Department of Cardiovascular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.

Aims: Early detection of aortic stenosis (AS) is becoming increasingly important with a better outcome after aortic valve replacement in asymptomatic severe AS patients and a poor outcome in moderate AS. We aimed to develop artificial intelligence-enabled electrocardiogram (AI-ECG) using a convolutional neural network to identify patients with moderate to severe AS.

Methods And Results: Between 1989 and 2019, 258 607 adults [mean age 63 ± 16.3 years; women 122 790 (48%)] with an echocardiography and an ECG performed within 180 days were identified from the Mayo Clinic database. Moderate to severe AS by echocardiography was present in 9723 (3.7%) patients. Artificial intelligence training was performed in 129 788 (50%), validation in 25 893 (10%), and testing in 102 926 (40%) randomly selected subjects. In the test group, the AI-ECG labelled 3833 (3.7%) patients as positive with the area under the curve (AUC) of 0.85. The sensitivity, specificity, and accuracy were 78%, 74%, and 74%, respectively. The sensitivity increased and the specificity decreased as age increased. Women had lower sensitivity but higher specificity compared with men at any age groups. The model performance increased when age and sex were added to the model (AUC 0.87), which further increased to 0.90 in patients without hypertension. Patients with false-positive AI-ECGs had twice the risk for developing moderate or severe AS in 15 years compared with true negative AI-ECGs (hazard ratio 2.18, 95% confidence interval 1.90-2.50).

Conclusion: An AI-ECG can identify patients with moderate or severe AS and may serve as a powerful screening tool for AS in the community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab153DOI Listing
August 2021

Assessment of left ventricular filling pressure with Doppler velocities across the patent foramen ovale.

J Echocardiogr 2021 Sep 12;19(3):158-165. Epub 2021 Jan 12.

Department of Cardiovascular Medicine, 200 First St SW, Rochester, MN, 55905, USA.

Background: The utility of Doppler velocities across the patent foramen ovale (PFO) to estimate left ventricular (LV) filling pressure is not well known.

Methods: The best cut-off value of peak interatrial septal velocity across a transeptal puncture site measured by transesophageal echocardiography for estimating high mean left atrial (LA) pressure (≥ 15 mmHg) was determined in 17 patients. This cut-off value was subsequently applied to 67 patients with a PFO undergoing transthoracic echocardiography (TTE) for assessing the value of PFO velocity in determining LV filling pressure.

Results: The peak systolic interatrial septal velocities significantly correlated with directly measured mean LA pressures during transcatheter mitral valve procedure (r = 0.77, P < 0.001). The best cut-off value was 1.7 m/s for predicting high LA pressure (AUC 0.91; sensitivity 90%, specificity 86%). When this cut-off was applied to patients undergoing TTE, peak PFO velocity ≥ 1.7 m/s correlated with reduced e', higher E/e', and higher tricuspid regurgitation velocity (P < 0.01). LV filling pressure according to the 2016 diastolic guideline was compared with peak PFO velocity in 51 patients. Among patients with high filling pressure according to the guidelines (n = 20), peak PFO velocity ≥ 1.7 m/s was present in 60% of patients. In patients with normal filling pressure per the guidelines (n = 31), PFO velocity < 1.7 m/s was present 84%. Sensitivity and specificity were 75% and 92%, respectively, in patients with sinus rhythm, but were only 50% and 57%, respectively, among patients with atrial fibrillation.

Conclusions: Doppler-derived peak PFO velocities could be valuable in the assessment of increased LV filling pressure using 1.7 m/s as the cut-off value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12574-020-00509-2DOI Listing
September 2021

Prognostic Risk Stratification of Patients with Moderate Aortic Stenosis.

J Am Soc Echocardiogr 2021 03 5;34(3):248-256. Epub 2020 Nov 5.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Background: Currently risk stratification of moderate aortic stenosis (AS) is still incipient. The aim of this study was to identify prognostic factors in patients with moderate AS.

Methods: The prognosis of patients with moderate AS (1 < aortic valve area ≤ 1.5 cm) stratified by left ventricular ejection fraction (LVEF; 50%), stroke volume index (SVI; 35 mL/m), and elevated E/e' ratio (average, 14) was compared with that of the age- and sex-matched general population.

Results: Of 696 patients (median age, 77 years; aortic valve area 1.3 cm; 57% men), 279 (40%) died during a median follow-up period of 3.4 years. Mortality was higher in patients with moderate AS than reference (mortality ratio, 2.43; 95% CI, 2.17-2.72). LVEF < 50%, SVI < 35 mL/m, and elevated E/e' ratio were present in 113 (17%), 54 (8%), and 330 (54%) patients; mortality ratios were 3.89 (95% CI, 3.07-4.85), 6.40 (95% CI, 4.57-8.71), and 2.58 (95% CI, 2.21-3.00), respectively. Even if LVEF or SVI was preserved, the mortality ratio was more than twice than reference (P < .001), but elevated E/e' ratio could discriminate additional patients at higher risk (hazard ratio [HR], 2.71; 95% CI, 1.88-3.91). Two hundred one patients (29%) underwent aortic valve replacement at a median of 2.3 years after the diagnosis of moderate AS. LVEF < 50% (HR, 2.98; 95% CI, 1.39-6.56), SVI < 35 mL/m (HR, 3.34; 95% CI, 1.02-10.90) and elevated E/e' ratio (HR, 2.73; 95% CI, 1.26-5.94) were all associated with worse prognosis even if aortic valve replacement was performed.

Conclusions: In patients with moderate AS, those with decreased LVEF and/or SVI are at high risk. Even if these parameters are preserved, patients with elevated E/e' ratios are at intermediate risk. Further investigation is warranted to assess whether earlier intervention could improve outcomes and reduced cardiac-related death among patients at high and intermediate risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.echo.2020.10.012DOI Listing
March 2021

Left Ventricular Global Longitudinal Strain Is Associated With Long-Term Outcomes in Moderate Aortic Stenosis.

Circ Cardiovasc Imaging 2020 04 9;13(4):e009958. Epub 2020 Apr 9.

Department of Cardiovascular Medicine (D.Z., S.I., W.R.M., V.T.N., S.V.P., H.R.V., P.A.P., J.K.O.), Mayo Clinic, Rochester, MN.

Background: Left ventricular global longitudinal strain (GLS) is associated with long-term outcomes of patients with severe aortic stenosis. However, its prognostic value in patients with moderate aortic stenosis remains unknown.

Methods: Patients diagnosed with moderate aortic stenosis (1.0< aortic valve area ≤1.5 cm) and left ventricular ejection fraction ≥50% were identified. GLS was assessed by 2-dimensional strain imaging using speckle-tracking method. All-cause mortality was assessed according to the median GLS value.

Results: Two hundred eighty-seven patients were included (median age 76 years; 47% male). Mean aortic valve area was 1.25 cm, left ventricular ejection fraction 62%, and median GLS -15.2%. During a median follow-up of 3.9 years, there were 103 deaths (36%). Mortality was higher in patients with GLS>-15.2% (hazard ratio 2.62 [95% CI 1.69-4.06]) compared with patients with GLS ≤-15.2% even after adjusting for confounders. Mortality rates at 1, 3, 5 years were 21%, 35%, 48%, respectively, in patients with GLS >-15.2%, and 6%, 15%, 19% in those with GLS ≤-15.2%. Even among those with left ventricular ejection fraction ≥60%, GLS discriminated higher-risk patients (=0.0003). During follow-up, 106 (37%) patients underwent aortic valve replacement with median waiting-time of 2.4 years, and their survival was better than patients without aortic valve replacement. Among those patients undergoing aortic valve replacement, prognosis was still worse in patients with GLS >-15.2% (=0.04). Mortality rates at 1, 3, 5 years were 2%, 10%, 20%, respectively, in patients with GLS >-15.2% and 2%, 5%, 6% in those with GLS ≤-15.2%.

Conclusions: Impaired GLS in moderate aortic stenosis patients is associated with higher mortality rates even among those undergoing aortic valve replacement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCIMAGING.119.009958DOI Listing
April 2020

Prognostic Value of N-Terminal Pro-form B-Type Natriuretic Peptide in Patients With Moderate Aortic Stenosis.

Am J Cardiol 2020 05 11;125(10):1566-1570. Epub 2020 Feb 11.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Plasma B-type natriuretic peptide (BNP) and its N-terminal pro-form, NT-proBNP, can predict outcomes in patients with severe aortic stenosis (AS). However, their prognostic value in moderate AS is currently unknown. The present study included 261 patients diagnosed with moderate AS (1.0 888 pg/dl). During a median follow up of 2.7 years, there were 136 (52%) deaths. Mortality rate was much higher in patients with higher-median NT-pro BNP compared to those with lower-median NT-pro BNP levels (p <0.001). Higher-median NT-pro BNP level was significantly associated with higher mortality rate (hazard ratio 3.11; 95% confidence interval 1.78 to 5.46, p <0.001) even after adjusting for confounders. Aortic valve replacement (AVR) was performed in 82 (31%) patients and median time to AVR was 2.1 years. Patients with higher-median NT-pro BNP had higher mortality rate compared to patients with lower-median NT-pro BNP even after AVR (p <0.01). In conclusion, higher NT-proBNP level is associated with higher mortality rates in patients with moderate AS even among those undergoing AVR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2020.02.004DOI Listing
May 2020

Impact of Stroke Volume Index and Left Ventricular Ejection Fraction on Mortality After Aortic Valve Replacement.

Mayo Clin Proc 2020 01;95(1):69-76

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To assess the impact of stroke volume index (SVI) and left ventricular ejection fraction (LVEF) on prognosis in patients with severe aortic stenosis, comparing those undergoing transcatheter aortic valve replacement (TAVR) and those with surgical AVR (SAVR).

Patients And Methods: A total of 742 patients from the CoreValve US Pivotal High-Risk Trial randomized to TAVR (n=389) or SAVR (n=353) from February 2011 to September 2012 were stratified by an SVI of 35 mL/m and LVEF of 50% for comparing all-cause mortality at 1 year.

Results: The prevalence of an SVI of less than 35 mL/m in patients who underwent TAVR and SAVR was 35.8% (125 of 349) and 31.3% (96 of 307), respectively; LVEF of less than 50% was present in 18.1% (63 of 348) and 19.6% (60 of 306), respectively. Among patients with an SVI of less than 35 mL/m, 1-year mortality was similar between patients with TAVR and SAVR (16.3% vs 22.2%; P=.25). However, in those with an SVI of 35 mL/m or greater, 1-year mortality was lower in those with TAVR than SAVR (10.3% vs 17.3%; P=.03). In patients with an LVEF of less than 50%, mortality was not affected by AVR approach (P>.05). In patients with an LVEF of 50% or higher, TAVR was associated with lower mortality than SAVR when SVI was preserved (9.8% vs 18.6%; P=.01). Mortality was not affected by SVI within the same AVR approach when LVEF was 50% or higher.

Conclusion: In patients with severe aortic stenosis at high risk, there is a significant interaction between AVR approach and the status of SVI and LVEF. When LVEF or SVI was reduced, prognosis was similar regardless of AVR approach. In those with preserved LVEF or SVI, TAVR was associated with a better prognosis than SAVR.

Trial Registration: clinicaltrials.gov Identifier: NCT01240902.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2019.10.031DOI Listing
January 2020

Sex Difference in Left Ventricular Response to Aortic Stenosis.

Authors:
Jae K Oh Saki Ito

JACC Cardiovasc Imaging 2020 03 18;13(3):712-714. Epub 2019 Sep 18.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2019.08.012DOI Listing
March 2020

Efficacy of an electrochemical flow cell introduced into the electrochemical Fenton-type process using a Cu(I)/HOCl system.

Water Sci Technol 2019 Jul;80(1):184-190

De Nora Permelec Ltd, 24-6 Higashitakasaki, Tamamo 706-0134, Japan.

An electrochemical flow cell was introduced into the electrochemical Fenton-type process using a Cu(I)/HOCl system. The effects of the current density and the initial cupric ion (Cu) concentration on the process performance were discussed. The current efficiency of the process improved from 6.1% for an electrolytic tank system to 33% for the electrochemical flow cell system at a current density of 5.0 mA/cm and an initial Cu concentration of 1.0 mM. The current efficiency increased to 58% for Cu concentrations of 2.0 mM and beyond. The cathodic reduction of Cu to the cuprous ion (Cu) emerged as the rate-determining step in comparison to the anodic production of free chlorine. The introduction of the electrochemical flow cell enhanced the cathodic production of Cu by reinforcing the mass transfer of the Cu to the cathode, and the detachment of micro bubbles generated electrochemically at the cathode surface. A decrease in the current density and an increase in the initial Cu concentration also improved the current efficiency by promoting the cathodic production of Cu. This involved the prevention of the cathodic reduction of protons to hydrogen gas and the elevation of the electrode potential of the cathodic reaction from Cu to Cu.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2166/wst.2019.267DOI Listing
July 2019

Finite Element Method Analysis of Compression Fractures on Whole-Spine Models Including the Rib Cage.

Comput Math Methods Med 2019 5;2019:8348631. Epub 2019 May 5.

Faculty of Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube, Yamaguchi 755-8611, Japan.

Spinal compression fractures commonly occur at the thoracolumbar junction. We have previously constructed a 3-dimensional whole-spine model from medical images by using the finite element method (FEM) and then used this model to develop a compression fracture model. However, these models lacked the rib cage. No previous study has used whole-spine models including the rib cage constructed from medical images to analyze compression fractures. Therefore, in this study, we added the rib cage to whole-spine models. We constructed the models, including a normal spine model without the rib cage, a whole-spine model with the rib cage, and whole-spine models with compression fractures, using FEM analysis. Then, we simulated a person falling on the buttocks to perform stress analysis on the models and to examine to what extent the rib cage affects the analysis of compression fractures. The results showed that the intensity of strain and the vertebral body with minimum principle strain differed between the spine model including the rib cage and that excluding the rib cage. The strain on the spine model excluding the rib cage had approximately twice the intensity of the strain on the spine model including the rib cage. Therefore, the rib cage contributed to the stability of the thoracic spine, thus preventing deformation of the upper thoracic spine. However, the presence of the rib cage increased the strain around the site of compression fracture, thus increasing the possibilities of a refracture and fractures of adjacent vertebral bodies. Our study suggests that the analysis using spine models including the rib cage should be considered in future investigations of disorders of the spine and internal fracture fixation. The development of improved models may contribute to the improvement of prognosis and treatment of individual patients with disorders of the spine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/8348631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525900PMC
January 2020

The Authors Reply.

JACC Cardiovasc Imaging 2019 06;12(6):1116

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2019.04.008DOI Listing
June 2019

Total Synthesis of Termicalcicolanone A via Organocatalysis and Regioselective Claisen Rearrangement.

Org Lett 2019 04 8;21(8):2777-2781. Epub 2019 Apr 8.

Department of Materials and Life Sciences, Faculty of Science and Technology , Sophia University , 7-1 Kioicho , Chiyoda-ku, Tokyo 102-8554 , Japan.

A total synthesis of an anticancer xanthone natural product termicalcicolanone A utilizing multiple nucleophilic aromatic substitutions and pericyclic reactions has been developed. The pyrano[3,2- b]xanthen-6-one scaffold was constructed via NHC-catalyzed aroylation to produce the benzophenone intermediate, Claisen cyclization to form the pyran ring, and intramolecular 1,4-addition to construct the xanthone framework. The prenyl group was introduced in the final stages of the synthesis through regioselective Claisen rearrangement. The synthesis has been achieved in 19 steps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b00731DOI Listing
April 2019

Left Ventricular Contractility and Wall Stress in Patients With Aortic Stenosis With Preserved or Reduced Ejection Fraction.

JACC Cardiovasc Imaging 2020 02 13;13(2 Pt 1):357-369. Epub 2019 Mar 13.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Objectives: This study sought to determine the prevalence of reduced contractility and uncompensated wall stress in patients with aortic stenosis (AS) with preserved or reduced left ventricular ejection fraction (LVEF) and their impact on survival.

Background: LVEF in AS is determined not only by contractility but also by loading conditions.

Methods: Patients with first diagnosis (time 0) of severe AS (aortic valve area [AVA]≤1 cm) with prior echo study (-3±1 years) were identified. Contractility was evaluated by plotting midwall fractional shortening (mFS) against circumferential end-systolic wall stress (cESS), stratified by LVEF of 60% at time 0. The temporal changes (from -3 years to time 0) and prognostic value of LVEF, contractility, and wall stress were assessed.

Results: Of 445 patients, 290 (65%) had LVEF ≥60% (median: 66% [interquartile range {IQR}: 63% to 69%]) and 155 patients (35%) had LVEF <60% (median: 47% [IQR: 34% to 55%]). Median AVA was 1.27 cm (IQR: 1.13 to 1.43 cm) at -3 years and 0.90 cm (IQR: 0.83 to 0.96 cm) at time 0. Decreased contractility was already present at -3 years (49 [17%] vs. 59 [38%]; LVEF ≥60% vs. <60%; p < 0.001) and became more prevalent at time 0 (69 [24%] vs. 106 [68%]; p < 0.001). Overall, wall stress was well controlled in both groups at -3 years (1 [0%] vs. 12 [8%]; p < 0.001) but deteriorated over time in patients with LVEF <60% (time 0: 0 [0%] vs. 26 [17%]; p < 0.001). During a median follow-up of 3.4 years, LVEF <60%, decreased contractility and high wall stress were associated with worse survival (p < 0.01 for all). Decreased contractility remained incremental to LVEF in patients with LVEF ≥60% (p < 0.01), but less so when LVEF was <60% (p = 0.11).

Conclusions: In patients with severe AS, LVEF <60% is associated with a poor prognosis, being linked with decreased contractility and/or high wall stress. Decreased contractility is also present in a subset of patients with LVEF ≥60% and provides incremental prognostic value. These abnormalities already exist before AVA reaches 1.0 cm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2019.01.009DOI Listing
February 2020

Reduced Left Ventricular Ejection Fraction in Patients With Aortic Stenosis.

J Am Coll Cardiol 2018 03;71(12):1313-1321

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Left ventricular ejection fraction (LVEF) is reduced in a subset of patients with severe aortic stenosis (AS).

Objectives: The authors sought to determine the temporal course of reduced LVEF, its predictors, and its impact on prognosis in severe AS.

Methods: Serial echocardiograms of 928 consecutive patients with first-time diagnosis of severe AS (aortic valve area [AVA] ≤1 cm) who had at least 1 echocardiogram before the diagnosis were evaluated. A total of 3,684 echocardiograms (median 3 studies per patient) within the preceding 10 years were analyzed.

Results: At the initial diagnosis, 196 (21%) patients had an LVEF <50% (35.1 ± 9.7%) and 732 (79%) had an LVEF ≥50% (64.2 ± 6.1%). LVEF deterioration had begun before AS became severe for those with an LVEF <50% and accelerated after AVA reached 1.2 cm, whereas mean LVEF remained >60% in patients with LVEF ≥50% at initial diagnosis. The strongest predictor for LVEF deterioration was LVEF <60% at 3 years before AS became severe (odds ratio: 0.86; 95% confidence interval: 0.83 to 0.89; p < 0.001). During the median follow-up of 3.3 years, mortality was significantly worse, not only for patients with an LVEF <50%, but for patients with an LVEF of 50% ≤ LVEF <60% compared with patients with an LVEF ≥60% even after aortic valve replacement (p < 0.001).

Conclusions: In patients with severe AS and reduced LVEF, a decline in LVEF began before AS became severe and accelerated after AVA reached 1.2 cm. LVEF <60% in the presence of moderate AS predicts further deterioration of LVEF and appears to represent abnormal LVEF in AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2018.01.045DOI Listing
March 2018

Finite element analysis of compression fractures at the thoracolumbar junction using models constructed from medical images.

Exp Ther Med 2018 Apr 7;15(4):3225-3230. Epub 2018 Feb 7.

Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.

Vertebral fractures commonly occur at the thoracolumbar junction. These fractures can be treated with mild residual deformity in many cases, but are reportedly associated with increased risk of secondary vertebral fractures. In the present study, a three-dimensional (3D) whole spine model was constructed using the finite element method to explore the mechanism of development of compression fractures. The 3D model of the whole spine, from the cervical spine to the pelvis, was constructed from computed tomography (CT) images of an adult male. Using a normal spine model and spine models with compression fractures at the T11, T12 or L1 vertebrae, the distribution of strain was analyzed in the vertebrae after load application. The normal spine model demonstrated greater strain around the thoracolumbar junction and the middle thoracic spine, while the compression fracture models indicated focused strain at the fracture site and adjacent vertebrae. Increased load time resulted in the extension of the strain region up to the middle thoracic spine. The present findings, that secondary vertebral fractures commonly occur around the fracture site, and may also affect the thoracic vertebrae, are consistent with previous clinical and experimental results. These results suggest that follow-up examinations of compression fractures at the thoracolumbar junction should include the thoracic spine and adjacent vertebrae. The current data also demonstrate that models created from CT images can be used for various analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2018.5848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841061PMC
April 2018

Novel GLI3 variant causing overlapped Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS) phenotype with agenesis of gallbladder and pancreas.

Diagn Pathol 2018 Jan 3;13(1). Epub 2018 Jan 3.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime, 791-0295, Japan.

Background: A proper balance between the activator and the repressor form of GLI3, a zinc-finger transcription factor downstream of hedgehog signaling, is essential for proper development of various organs during development. Mutations in different domains of the GLI3 gene underlie several congenital diseases including Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS).

Case Presentation: Here, we describe the case of an overlapped phenotype of these syndromes with agenesis of the gallbladder and the pancreas, bearing a c.2155 C > T novel likely pathogenic variant of GLI3 gene by missense point mutation causing p.P719S at the proteolytic cleavage site.

Conclusions: Although agenesis of the gallbladder and the pancreas is uncommon in GLI3 morphopathy, a slight difference in the gradient or the balance between activator and repressor in this case may hinder sophisticated spatial and sequential hedgehog signaling that is essential for proper development of gallbladder and pancreas from endodermal buds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13000-017-0682-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389258PMC
January 2018

Factors Influencing the Prognosis of Octogenarians with Aortic Stenosis in the Advanced Aging Societies.

Intern Med 2016 1;55(17):2351-8. Epub 2016 Sep 1.

Division of Cardiology and Department of Laboratory Medicine, Shimane University Faculty of Medicine, Japan.

Objective The recognition of clinical symptoms is critical to developing an effective therapeutic strategy for aortic valve stenosis (AS). Although AS is common, little is known about the factors influencing the natural history of AS patients who are 80 years of age older in advanced aging societies. We investigated the natural history and indications for valve procedures in AS patients of 80 years of age or older. Methods The medical records of 108 consecutive AS patients (moderate grade or higher) who are 80 years of age or older (mean age, 84.2±3.9 years; female, 65 patients) were reviewed to investigate their symptoms, the development of congestive heart failure, the incidence of referral for aortic valve replacement and death. The median duration of follow-up was 9 months (interquartile range, 2 to 25 months). Results The probability of remaining free of events (valve replacement and death) was 29±13% in all patients. There was no significant difference in the aortic valve area of the symptomatic and asymptomatic patients (0.85±0.28 cm(2) vs. 0.88±0.25 cm(2), p=0.59). The aortic valve (AV) velocity and AV area index were predictors of subsequent cardiac events (p<0.05). Conclusion The severity of AS was the only factor to affect the prognosis of AS patients who were 80 years old of age or older. It is necessary to frequently monitor the subjective symptoms of such patients and to objectively measure the AV area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.55.6691DOI Listing
March 2017

Impact of right ventricular size and function on survival following transcatheter aortic valve replacement.

Int J Cardiol 2016 Oct 6;221:269-74. Epub 2016 Jul 6.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: The impact of pre-procedural RV size and function on outcomes following transcatheter aortic valve replacement (TAVR) is not well established. The aim of this study was to investigate the role of right ventricular size and function on outcomes following TAVR.

Methods And Results: Between November 2008 and June 2013, 268 consecutive patients (age 80.5±7.9years, aortic valve area 0.79±0.16cm(2)) with symptomatic severe aortic stenosis (AS) undergoing TAVR at Mayo Clinic were included. Transthoracic echocardiographic quantitative and semiquantitative assessment of RV chamber size and systolic function was performed and included tricuspid annular plane systolic excursion (TAPSE), RV systolic excursion velocity (S'), fractional area change (FAC), RV index of myocardial performance (RIMP). The primary endpoint of all-cause mortality after TAVR was measured and observed in 65 patients (median follow up duration: 412days). Univariate analysis identified semiquantitative RV dilatation (p<0.001) and systolic dysfunction (p=0.013), RV basal dimension (p=0.003) and RV outflow proximal dimension (p=0.031) to be of prognostic significance. After multivariate adjustment, patients with semiquantitative RV dilatation (HR 2.61, 95% CI 1.45-4.65, p=0.002) and larger RV basal dimension (HR 1.07, 95% CI per mm 1.02-1.11, p=0.007) had significantly worse survival even after adjusting for age, sex, Society of Thoracic Surgeons (STS) risk score, left ventricular ejection fraction, tricuspid regurgitation, pulmonary artery systolic pressure, and atrial fibrillation.

Conclusion: RV dilatation is an important determinant of postoperative outcomes in patients undergoing TAVR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2016.07.085DOI Listing
October 2016

Identification of a Potent and Selective GPR4 Antagonist as a Drug Lead for the Treatment of Myocardial Infarction.

ACS Med Chem Lett 2016 May 24;7(5):493-7. Epub 2016 Feb 24.

Faculty of Pharmaceutical Science, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.

GPR4, a pH-sensing G protein-coupled receptor, is highly expressed in endothelial cells and may be activated in myocardial infarction due the decreased tissue pH. We are interested in GPR4 antagonists as potential effective pharmacologic tools and/or drug leads for the treatment of myocardial infarction. We investigated the structure-activity relationship of a known GPR4 antagonist 1 as a lead compound to identify 3b as the first potent and selective GPR4 antagonist, whose effectiveness was demonstrated in a mouse myocardial infarction model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsmedchemlett.6b00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867472PMC
May 2016

Characterization of Imidazopyridine Compounds as Negative Allosteric Modulators of Proton-Sensing GPR4 in Extracellular Acidification-Induced Responses.

PLoS One 2015 12;10(6):e0129334. Epub 2015 Jun 12.

Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.

G protein-coupled receptor 4 (GPR4), previously proposed as the receptor for sphingosylphosphorylcholine, has recently been identified as the proton-sensing G protein-coupled receptor (GPCR) coupling to multiple intracellular signaling pathways, including the Gs protein/cAMP and G13 protein/Rho. In the present study, we characterized some imidazopyridine compounds as GPR4 modulators that modify GPR4 receptor function. In the cells that express proton-sensing GPCRs, including GPR4, OGR1, TDAG8, and G2A, extracellular acidification stimulates serum responsive element (SRE)-driven transcriptional activity, which has been shown to reflect Rho activity, with different proton sensitivities. Imidazopyridine compounds inhibited the moderately acidic pH-induced SRE activity only in GPR4-expressing cells. Acidic pH-stimulated cAMP accumulation, mRNA expression of inflammatory genes, and GPR4 internalization within GPR4-expressing cells were all inhibited by the GPR4 modulator. We further compared the inhibition property of the imidazopyridine compound with psychosine, which has been shown to selectively inhibit actions induced by proton-sensing GPCRs, including GPR4. In the GPR4 mutant, in which certain histidine residues were mutated to phenylalanine, proton sensitivity was significantly shifted to the right, and psychosine failed to further inhibit acidic pH-induced SRE activation. On the other hand, the imidazopyridine compound almost completely inhibited acidic pH-induced action in mutant GPR4. We conclude that some imidazopyridine compounds show specificity to GPR4 as negative allosteric modulators with a different action mode from psychosine, an antagonist susceptible to histidine residues, and are useful for characterizing GPR4-mediated acidic pH-induced biological actions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129334PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466532PMC
April 2016

Visually confirmed post-systolic shortening during the recovery period in four cases of Takotsubo cardiomyopathy.

J Echocardiogr 2014 12 1;12(4):159-61. Epub 2014 Nov 1.

Division of Cardiology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.

We report visually confirmed post-systolic shortening (PSS) during the recovery period and the relationship between PSS and electrocardiographic abnormalities in 4 cases of Takotsubo cardiomyopathy (TTC). In these 4 cases, the appearance of visually confirmed PSS during the recovery period coincided with observation of the deepest T wave and the longest QT interval. The transmural repolarization gradient and heterogeneous duration of myocardial contractions may cause PSS in the TTC recovery period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12574-014-0231-3DOI Listing
December 2014

A case of ascending aortic dissection and rupture caused by giant cell arteritis.

Int Heart J 2014 7;55(6):555-9. Epub 2014 Oct 7.

Division of Cardiology, Shimane University Faculty of Medicine.

Giant cell arteritis (GCA) is an autoimmune disease characterized by granulomatous inflammation in the wall of medium-sized and large-sized arteries, and it usually occurs in patients over 50 years of age.(1)) Symptoms are nonspecific, and include fatigue, fever, and headache.(2)) It is occasionally combined with aortic complications, and ruptures resulting in death. These complications occur as late events, usually several years after diagnosis and often after other symptoms have subsided.(3)) Physicians should therefore be alert for complications of the large arteries in GCA. Here we present a case of GCA combined with ascending aortic dissection and rupture 3 weeks after diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1536/ihj.14-059DOI Listing
January 2015

A case with myxoma of the left ventricular outflow tract.

J Cardiol Cases 2014 Jul 29;10(1):13-15. Epub 2014 Apr 29.

Division of Cardiology, Shimane University Faculty of Medicine, Izumo, Japan.

Left ventricular (LV) myxomas are rare. We present a case of a LV myxoma arising from the interventricular septum of the LV outflow tract in a 76-year-old woman. General examination of the patient did not reveal any abnormality except for a grade 3/6 systolic murmur in the left parasternal area. Transthoracic echocardiography revealed a round pedunculated mass (size, 23 mm × 11 mm × 10 mm) at the interventricular septum with a broad pedicle. The mass was successfully removed and was pathologically confirmed to be a myxoma. < This is the rare case of left ventricular (LV) myxoma arising from LV outflow tract, which was pathologically confirmed.>.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jccase.2014.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278682PMC
July 2014

Left atrial remodeling and recurrence of congestive heart failure in patients initially diagnosed with heart failure.

Echocardiography 2014 Sep 24;31(8):936-40. Epub 2013 Dec 24.

Division of Cardiology, Shimane University Faculty of Medicine, Izumo, Japan.

Background: Left atrial volumes (LAVs) have been suggested to represent long-term exposure to elevated pressures. This study examined the recurrence of heart failure (HF) based on LAV in patients initially diagnosed with congestive HF (CHF).

Methods: This study comprised 77 patients (age, 75 ± 8 years) with well-documented, clinically defined HF, and complete two-dimensional echocardiographic examinations. The echocardiographic examinations were performed on admission and after medical treatment (90 ± 43 days after initial examination). Patients with atrial fibrillation, flail mitral valve, or mitral valve replacement were excluded from this study.

Results: The initial left ventricular ejection fraction (LVEF) was 44 ± 17% and the indexed LAV (LAVI) was 61 ± 22 mL/m(2) . After medical treatment, a decreased LAVI was observed in 38 patients and an increased LAVI (LA remodeling) was observed in 39 patients. With median follow-up periods of 454 days, compared to patients with decreased LAVI, patients with LA remodeling had a significantly higher incidence of CHF recurrence (P = 0.008). Patients with LA remodeling had a CHF-free survival rate of 36 ± 13% vs. 81 ± 9% (those without LA remodeling). A multivariate analysis indicated that, follow-up LV end-systolic volume (P = 0.04), LVEF (P = 0.005) and LAVI (P = 0.04) independently predicted CHF recurrence.

Conclusions: Patients initially diagnosed with CHF follow divergent courses based on their LAV. LA remodeling after medical treatment can be useful for predicting CHF recurrence during follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/echo.12497DOI Listing
September 2014

A case of arrhythmogenic right ventricular cardiomyopathy in a 70-year-old patient.

J Med Ultrason (2001) 2014 Jan 18;41(1):73-6. Epub 2013 May 18.

Division of Cardiology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, 693-8501, Japan.

A 70-year-old man was admitted because of syncope and dyspnea. Two months before admission, exertional dyspnea occurred with syncope. Ventricular tachycardia with a monomorphic left bundle-branch block configuration was detected. An echocardiographic examination showed severe dilatation and diffuse, severe hypokinesis of the right ventricle, with thrombus formation in the right ventricular apex. Based on the clinical picture, the patient was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC). This case emphasizes the need for early identification of RV abnormalities in patients with ARVC to determine appropriate therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10396-013-0455-2DOI Listing
January 2014

Trousseau syndrome with nonbacterial thrombotic endocarditis in a patient with uterine cancer.

Intern Med 2013 ;52(12):1353-8

Division of Cardiology, Shimane University Faculty of Medicine, Japan.

This paper aims to describe the usefulness of transthoracic echocardiography in the follow-up of recurrent nonbacterial thrombotic endocarditis (NBTE) associated with neoplastic conditions. A 60-year-old woman with advanced uterine cancer developed recurrent areas of aseptic vegetation on the mitral valve along with cerebral, renal and splenic embolisms. Echocardiographic assessments revealed vegetation and thrombotic events on three occasions. In this case, transthoracic echocardiography was effective in following the decreased frequency of attachment of the NBTE vegetation to the mitral valve and reductions in the size of the area of vegetation following treatment with unfractionated heparin infusion, hysterectomy and chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.52.9384DOI Listing
February 2014

Impairment of platelet retention rate in patients with severe aortic valve stenosis.

J Cardiol 2013 Sep 2;62(3):171-5. Epub 2013 Jun 2.

Fourth Department of Internal Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo City, Shimane 693-8501, Japan. Electronic address:

Background: Recent reports revealed the presence of acquired von Willebrand syndrome type 2A in patients with aortic valve stenosis (AS). von Willebrand factor (vWF) has been shown to play a vital role in platelet adhesion. Therefore, we measured the platelet retention rates, which reflect platelet adhesion, in patients with severe AS.

Methods: In addition to echocardiography, routine blood screening tests were performed and the platelet retention rates were measured using collagen-coated bead columns in 21 patients with severe AS and in 21 control subjects.

Results: Patients with severe AS showed the maximum aortic valve pressure gradients of 110.9±22.7 mmHg, and effective orifice areas of 0.59±0.20 cm2. The results of routine blood tests in patients with severe AS were comparable to those of control subjects; however, the platelet retention rates in the AS patients (7.3±5.0%) were significantly lower than those in control subjects (30.5±11.8%, p<0.001). A significant negative correlation was observed between maximum aortic valve pressure gradients and platelet retention rates (r = -0.81, p<0.001). In 8 patients with severe AS, the platelet retention rates increased from 5.8±3.6% to 16.0±2.4% after aortic valve replacement (p<0.001).

Conclusion: These findings suggest that impairment of platelet retention rate is seen in almost all patients with severe AS. Clinicians should be aware of the possibilities of vWF-mediated platelet dysfunction and bleeding tendency in patients with severe AS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2013.04.002DOI Listing
September 2013

Fluorescent-based methods for gene knockdown and functional cardiac imaging in zebrafish.

Mol Biotechnol 2013 Oct;55(2):131-42

Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

A notable advantage of zebrafish as a model organism is the ease of gene knockdown using morpholino antisense oligonucleotide (MO). However, zebrafish morphants injected with MO for a target protein often show heterogeneous phenotypes, despite controlling the injection volume of the MO solution in all embryos. We developed a method for estimating the quantity of MO injected into each living morphant, based on the co-injection of a control MO labeled with the fluorophore lissamine. By applying this method for knockdown of cardiac troponin T (tnnt2a) in zebrafish, we could efficiently select the partial tnnt2a-depleted zebrafish with a decreased heart rate and impairment of cardiac contraction. To investigate cardiac impairment of the tnnt2a morphant, we performed fluorescent cardiac imaging using Bodipy-ceramide. Cardiac image analysis showed moderate reduction of tnnt2a impaired diastolic distensibility and decreased contraction and relaxation velocities. To the best of our knowledge, this is the first report to analyze the role of tnnt2a in cardiac function in tnnt2a-depleted living animals. Our combinatorial approach can be applied for analyzing the molecular function of any protein associated with human cardiac diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12033-013-9664-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825550PMC
October 2013

A case of long QT syndrome having compound mutations of and .

J Cardiol Cases 2012 Dec 19;6(6):e170-e172. Epub 2012 Sep 19.

Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.

Long QT syndrome (LQTS) is a hereditary ion channelopathy resulting in prolonged cardiac repolarization and abnormal prolongation of the QT interval on the electrocardiogram (ECG). The patients are likely to develop ventricular arrhythmias and sudden cardiac death. Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. A 16-year-old-woman with QT prolongation on ECG had frequent syncopal episodes and an attack of ventricular tachycardia followed by ventricular fibrillation. The mutation (intravene sequence 4-1 c/t) in addition to the mutation (Arg56Gln) was identified. Her mother and older sister were also diagnosed as having LQTS, but had only a single mutation (). Her older sister had an episode of syncope, but her mother did not. Genetic analysis sometimes reveals 2 or more mutations in LQTS patients with clinical phenotypes of the Romano-Ward syndrome. Compound mutations in different LQTS-related genes are likely to modify clinical characteristics. In addition, comprehensive screening of LQTS-related genes might be needed when facing family members with different clinical manifestations. < Molecular biology and basic electrophysiology studies revealed an approach to the management of patients with LQTS, which includes genotype-based risk stratification. We described a case of LQTS having compound mutations of and who had frequent syncopal episodes and an attack of ventricular fibrillation. The mutations of 2 different genes were associated with a severe phenotype of LQTS. Comprehensive screening of LQTS-related genes might be needed for estimating the severity of LQTS.>.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jccase.2012.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269416PMC
December 2012

Single-beat determination of global longitudinal speckle strain in patients with atrial fibrillation.

J Echocardiogr 2012 Sep 26;10(3):90-4. Epub 2012 Jul 26.

Division of Cardiology, Shimane University Faculty of Medicine, 89-1 Enya-cyo, Izumo, 693-8501, Japan.

Background: Although global left ventricular (LV) systolic function is an important determinant of outcome, the assessment of global longitudinal speckle strain (GLS) in patients with atrial fibrillation (AF) is unreliable because of beat-to-beat variation. Previous studies have confirmed that LV contractility of each irregular beat is predicted from the ratio of preceding R-R (RR1) to pre-preceding R-R (RR2) intervals, and the value when the intervals are equal (RR1/RR2 = 1) estimates the average value of LV contractility. The aim of this study was to assess the clinical feasibility of an index that is obtained on the basis of the RR1/RR2 ratio for the estimation of GLS in patients with AF.

Methods: We evaluated the RR1/RR2 ratio for the measurement of GLS with apical 4-chamber views in 20 patients with AF. We obtained the GLS for ≥13 cardiac cycles, and the relationship between each GLS at a given cardiac beat and the RR1/RR2 ratio was evaluated by linear regression analysis. The value of GLS at RR1/RR2 = 1 was compared with the measured average value.

Results: The GLS showed a significant correlation with the RR1/RR2 ratio (r = -0.80). The calculated value of GLS at RR1/RR2 = 1 was quite similar to the average value (-10.17 ± 2.1 % vs. -10.06 ± 2.1 %). The GLS of a single beat with identical RR1 and RR2 intervals showed a significant correlation compared with the measured average value over all cardiac cycles (r = 0.94, y = 0.90x - 0.97).

Conclusions: The GLS at RR1/RR2 = 1 allows the LV systolic parameter to be accurately evaluated during AF and obviates the less reliable process of averaging multiple irregular beats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12574-012-0135-zDOI Listing
September 2012
-->