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Dive into the research topics where Yoshihiro Tanaka is active.

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Featured researches published by Yoshihiro Tanaka.


Circulation-arrhythmia and Electrophysiology | 2015

Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation

Kenshi Hayashi; Tetsuo Konno; Hayato Tada; Satoyuki Tani; Li Liu; Noboru Fujino; Atsushi Nohara; Akihiko Hodatsu; Toyonobu Tsuda; Yoshihiro Tanaka; Masa-aki Kawashiri; Hidekazu Ino; Naomasa Makita; Masakazu Yamagishi

Background—Few rare variants in atrial fibrillation (AF)–associated genes have been functionally characterized to identify a causal relationship between these variants and development of AF. We here sought to determine the clinical effect of rare variants in AF-associated genes in patients with lone AF and characterized these variants electrophysiologically and bioinformatically. Methods and Results—We screened all coding regions in 12 AF-associated genes in 90 patients with lone AF, with an onset of 47±11 years (66 men; mean age, 56±13 years) by high-resolution melting curve analysis and DNA sequencing. The potassium and sodium currents were analyzed using whole-cell patch clamping. In addition to using 4 individual in silico prediction tools, we extended those predictions to an integrated tool (Combined Annotation Dependent Depletion). We identified 7 rare variants in KCNA5, KCNQ1, KCNH2, SCN5A, and SCN1B genes in 8 patients: 2 of 8 probands had a family history of AF. Electrophysiological studies revealed that 2 variants showed a loss-of-function, and 4 variants showed a gain-of-function. Five of 6 variants with electrophysiological abnormalities were predicted as pathogenic by Combined Annotation Dependent Depletion scores. Conclusions—In our cohort of patients with lone AF, 7 rare variants in cardiac ion channels were identified in 8 probands. A combination of electrophysiological studies and in silico predictions showed that these variants could contribute to the development of lone AF, although further in vivo study is necessary to confirm these results. More than half of AF-associated rare variants showed gain-of-function behavior, which may be targeted using genotype-specific pharmacological therapy.


Circulation | 2014

Fragmented QRS Predicts Heart Failure Progression in Patients With Hypertrophic Cardiomyopathy

Akihiro Nomura; Tetsuo Konno; Takashi Fujita; Yoshihiro Tanaka; Yoji Nagata; Toyonobu Tsuda; Akihiko Hodatsu; Kenji Sakata; Hiroyuki Nakamura; Masa-aki Kawashiri; Noboru Fujino; Masakazu Yamagishi; Kenshi Hayashi

BACKGROUNDnAlthough fragmented QRS complex (frag-QRS) reflecting intra-ventricular conduction delay has been shown to be a prognostic marker for cardiac events, few data exist regarding the impact of frag-QRS on cardiac events in hypertrophic cardiomyopathy (HCM).nnnMETHODS AND RESULTSnNinety-four HCM patients (56 male; mean age, 58 ± 17 years) were retrospectively investigated. Frag-QRS was defined as the presence of various RsR patterns in at least 2 contiguous ECG leads. Major arrhythmic events (MAE) were defined as sudden cardiac death, and combined sustained ventricular tachycardia/ventricular fibrillation. New-onset atrial fibrillation (AF) was diagnosed based on ECG during provisional or routine medical examination. Heart failure (HF) with hospitalization was defined as hospital admission due to subjective or objective symptoms. Frag-QRS was detected in 31 patients (33%).TNNI3 was the most frequent disease-causing gene. Median follow-up was 4.6 years. The 4-year cumulative survival rates of cardiac death, MAE, new-onset AF and HF with hospitalization were 97.6%, 94.6%, 87.5% and 89.3%, respectively. On multivariate analysis, frag-QRS was significantly associated with HF with hospitalization (adjusted hazard ratios [95% confidence intervals]: 5.4 [1.2-36], P=0.03). Moreover, HF-free survival was significantly lower in the frag-QRS (+) group compared to the frag-QRS (-) group (79.0% vs. 95.1%, P=0.03).nnnCONCLUSIONSnFrag-QRS is associated with HF with hospitalization in HCM patients who had a unique distribution of gene mutations.


Atherosclerosis | 2015

Whole exome sequencing combined with integrated variant annotation prediction identifies asymptomatic Tangier disease with compound heterozygous mutations in ABCA1 gene.

Hayato Tada; Masa-aki Kawashiri; Atsushi Nohara; Reina Saito; Yoshihiro Tanaka; Akihiro Nomura; Tetsuo Konno; Kenji Sakata; Noboru Fujino; Toshinari Takamura; Akihiro Inazu; Hiroshi Mabuchi; Masakazu Yamagishi; Kenshi Hayashi

OBJECTIVEnMolecular diagnosis for subjects with extremely low HDL-C through candidate-gene approaches requires huge effort. Whole exome-sequencing (WES) has already shown approximately ∼30% success in the diagnosis of Mendelian disorders. Moreover, novel in silico prediction software for the pathogenicity of novel missense variants named Combined Annotation Dependent Depletion (CADD) has recently been developed, enabling the objective integration of many diverse annotations into a single measure (C-score) for each variant. Here, we investigated whether WES combined with integrated variant annotation prediction could facilitate the molecular diagnosis of this rare condition.nnnMETHODSnWES was performed on 8 individuals including 2 individuals exhibiting extremely low HDL-C (2xa0mg/dl and 6xa0mg/dl), 2 unaffected family members, and 4 unrelated individuals as controls. We filtered out the following variants: 1) Benign variants predicted by SnpEff; 2) Minor allele frequency (MAF)xa0>xa01%; 3) Segregation unmatched for the recessive form of inheritance; 4) C-scorexa0<xa010.nnnRESULTSnAmong 305,202 variants found in those individuals, we found 21,708 nonsense, missense, or splice site variants, of which 5192 were rare (MAFxa0≤xa01% or not reported). Filtering assuming a recessive pattern of inheritance, combined with the use of the C-score, successfully narrowed down the candidates to compound heterozygous mutations in the ABCA1 gene (c.6230Cxa0>xa0A or p.P2077H/c.6137Gxa0>xa0A or p.S2046N, and c.2842Gxa0>xa0A or p.G948R/c.1130Cxa0>xa0T or p.P377L).nnnCONCLUSIONSnWES combined with integrated variant annotation prediction successfully identified asymptomatic Tangier disease with novel ABCA1 mutations. This comprehensive approach is useful to determine causative variants, especially in recessive inherited diseases.


Journal of Cardiology | 2017

Prehospital predictors of neurological outcomes in out-of-hospital cardiac arrest patients aged 95 years and older: A nationwide population-based observational study

Akira Funada; Yoshikazu Goto; Tetsuo Maeda; Hayato Tada; Ryota Teramoto; Yoshihiro Tanaka; Kenshi Hayashi; Masakazu Yamagishi

BACKGROUNDnPopulation aging has rapidly progressed in Japan. However, few data exist regarding the characteristics of extremely elderly patients with out-of-hospital cardiac arrest (OHCA). We aimed to determine the prehospital predictors of one-month survival with favorable neurological outcomes (Cerebral Performance Category scale, category 1 or 2; CPC 1-2) in this population.nnnMETHODSnWe investigated 23,520 OHCA patients aged ≥95 years from a prospectively recorded, nationwide, Utstein-style Japanese database between 2008 and 2012. The primary study endpoint was one-month CPC 1-2 after OHCA.nnnRESULTSnThe one-month CPC 1-2 rate was 0.27% (63/23,520). Only two variables were significantly associated with one-month CPC 1-2 in a multivariate logistic regression model: prehospital return of spontaneous circulation (ROSC) [adjusted odds ratio (aOR), 94.4; 95% confidential interval (CI), 50.1-191.7] and emergency medical service (EMS)-witnessed arrest (aOR, 5.1; 95% CI, 2.6-10.2). When stratified by these two predictors, the one-month CPC 1-2 rates were 20.2% (18/89) for patients who had both prehospital ROSC and EMS-witnessed arrest, 4.2% (33/783) for those who had prehospital ROSC without EMS-witnessed arrest, 0.28% (3/1065) for those who had EMS-witnessed arrest without prehospital ROSC, and 0.04% (9/21,583) for those who had neither predictor, respectively.nnnCONCLUSIONSnThe crucial prehospital predictors for one-month CPC 1-2 in elderly OHCA patients aged ≥95 years in Japan were prehospital ROSC and EMS-witnessed arrest and the former was the predominant predictor.


American Journal of Cardiology | 2016

Prevalence of Type A Acute Aortic Dissection in Patients With Out-Of-Hospital Cardiopulmonary Arrest

Yoshihiro Tanaka; Kenji Sakata; Yasuo Sakurai; Tsuyoshi Yoshimuta; Yuka Morishita; Satoshi Nara; Isao Takahashi; Mitsugu Hirokami; Masakazu Yamagishi

Postmortem computed tomography (PMCT) has been recently reported to be useful for detecting causes of death in the emergency department. In this study, the incidence and causes of death of type A acute aortic dissection (AAD) were investigated in patients who experienced out-of-hospital cardiopulmonary arrest (OHCPA) using PMCT. PMCT or enhanced computed tomography was performed in 311 of 528 consecutive patients experiencing OHCPA. A total of 23 (7%) of 311 patients were diagnosed with type A AAD based on clinical courses and CT findings. Eighteen consecutive patients who did not experience OHCPA were diagnosed with type A AAD during the same period. Pre-hospital death was observed in 21 (51%) of 41 patients with type A AAD. Bloody pericardial effusion was observed more frequently in patients who experienced OHCPA with type A AAD than in those who did not experience OHCPA with type A AAD (91% vs 28%, respectively; p <0.05). In conclusion, the incidence of type A AAD was common (7%) in patients who experienced OHCPA, with a high rate of pre-hospital death. Aortic rupture to the intrapericardial space was considered the major cause of death in patients who experienced OHCPA with type A AAD.


Journal of Vascular Surgery | 2017

Clinical characteristics of spontaneous isolated visceral artery dissection

Yoshihiro Tanaka; Tsuyoshi Yoshimuta; Keiichi Kimura; Kenji Iino; Yudai Tamura; Kenji Sakata; Kenshi Hayashi; Hirofumi Takemura; Masakazu Yamagishi; Masa-aki Kawashiri

Objective: Spontaneous isolated visceral artery dissection (SIVAD) involving the celiac artery or superior mesenteric artery is rare, but it can be fatal. Given its rare incidence, the clinical characteristics of SIVAD are not fully understood. Therefore, the aim of this study was to investigate the clinical characteristics and prognosis of SIVAD. Methods: We retrospectively reviewed 39 consecutive patients diagnosed with SIVAD from January 2007 to December 2016. Demographic characteristics, symptoms, vital signs, blood examination results, and computed tomography findings were retrieved through medical record review. Results: The median age of the patients was 52 years; 94.9% were male, and 64.1% were symptomatic. Median follow‐up duration was 11 months. Overall, hypertension (48.7%) and smoking (79.5%) were frequently observed. There were significant differences between symptomatic and asymptomatic patients in white blood cell count and creatine kinase level but not in fibrin degradation products or D‐dimer level. There was a significant correlation between symptoms and length of dissection on computed tomography (P < .01). Conservative treatment was performed in 32 patients (82.1%), and only 7 patients required open surgery or intravascular intervention. Notably, the diameter of affected vessels decreased spontaneously with no rupture or symptom recurrence during follow‐up, and mortality was 0% at both 30 days and 1 year. Conclusions: The utility of blood examination, especially for fibrin degradation products and D‐dimer levels, for diagnosis of SIVAD is limited. A high index of suspicion is warranted in patients presenting with persistent severe abdominal pain. Conservative treatment should be considered first‐line therapy in patients without any signs of bowel ischemia or rupture.


JACC: Clinical Electrophysiology | 2017

J Waves for Predicting Cardiac Events in Hypertrophic Cardiomyopathy

Toyonobu Tsuda; Kenshi Hayashi; Tetsuo Konno; Kenji Sakata; Takashi Fujita; Akihiko Hodatsu; Yoji Nagata; Ryota Teramoto; Akihiro Nomura; Yoshihiro Tanaka; Hiroshi Furusho; Masayuki Takamura; Masa-aki Kawashiri; Noboru Fujino; Masakazu Yamagishi

OBJECTIVESnThis study sought to investigate whether the presence of J waves was associated with cardiac events in patients with hypertrophic cardiomyopathy (HCM).nnnBACKGROUNDnIt has been uncertain whether the presence of J waves predicts life-threatening cardiac events in patients with HCM.nnnMETHODSnThis study evaluated consecutive 338 patients with HCM (207 men; age 61 ± 17 years of age). A J-wave was defined as J-point elevation >0.1 mV in at least 2 contiguous inferior and/or lateral leads. Cardiac events were defined as suddenxa0cardiac death, ventricular fibrillation or sustained ventricular tachycardia, or appropriate implantable cardiac defibrillator therapy. The study also investigated whether adding the J-wave in a conventional risk model improved a prediction of cardiac events.nnnRESULTSnJ waves were seen in 46 (13.6%) patients at registration. Cardiac events occurred in 31 patients (9.2%) duringxa0median follow-up of 4.9 years (interquartile range: 2.6 to 7.1 years). In a Cox proportional hazards model, the presence of J waves was significantly associated with cardiac events (adjusted hazard ratio: 4.01; 95% confidence interval [CI]: 1.78 to 9.05; pxa0= 0.001). Compared with the conventional risk model, the model using J waves in addition to conventional risks better predicted cardiac events (net reclassification improvement, 0.55; 95% CI: 0.20 to 0.90; pxa0= 0.002).nnnCONCLUSIONSnThe presence of J waves was significantly associated with cardiac events in HCM. Adding J waves to conventional cardiac risk factors improved prediction of cardiac events. Further confirmatory studies are needed beforexa0considering J-point elevation as a marker of risk for use in making management decisions regarding risk in patients with HCM.


Heart and Vessels | 2017

T wave amplitude in lead aVR as a novel diagnostic marker for cardiac sarcoidosis

Yoshihiro Tanaka; Tetsuo Konno; Shohei Yoshida; Toyonobu Tsuda; Kenji Sakata; Hiroshi Furusho; Masayuki Takamura; Kenichi Yoshimura; Masakazu Yamagishi; Kenshi Hayashi

It is vital to identify cardiac involvement (CI) in patients with sarcoidosis as the condition could initially lead to sudden cardiac death. Although the T wave amplitude in lead aVR (TWAaVR) is reportedly associated with adverse cardiac events in various cardiovascular diseases, only scarce data are available concerning the utility of lead aVR in identifying CI in patients with sarcoidosis. We retrospectively investigated the diagnostic values of TWAaVR in patients with sarcoidosis in comparison with conventional electrocardiography parameters such as bundle branch block (BBB). From January 2006 to December 2014, 93 consecutive patients with sarcoidosis were enrolled (mean age, 55.7xa0±xa015.7xa0years; male, 31xa0%; cardiac involvement, nxa0=xa026). TWAaVR showed the greatest sensitivity (39xa0%) and specificity (92xa0%) in distinguishing between sarcoidosis patients with and without CI, at a cutoff value of −0.08xa0mV. The diagnostic value of BBB for cardiac involvement was significantly improved when combined with TWAaVR (sensitivity: 61–94xa0%, specificity: 97–89xa0%, area under the curve: 0.79–0.92, pxa0=xa00.018). Multivariate logistic regression analysis indicated that TWAaVR and BBB were independent electrocardiography parameters associated with CI. In summary, we observed that sarcoidosis patients exhibiting a high TWAaVR were likely to have CI. Thus, the application of a combination of BBB with TWAaVR may be useful when screening for CI in sarcoidosis patients.


Annals of Noninvasive Electrocardiology | 2017

Impact of T wave amplitude in lead aVR on predicting cardiac events in ischemic and nonischemic cardiomyopathy patients with an implantable cardioverter defibrillator

Yoshihiro Tanaka; Tetsuo Konno; Yudai Tamura; Toyonobu Tsuda; Hiroshi Furusho; Masayuki Takamura; Kenji Sakata; Masakazu Yamagishi; Kenshi Hayashi

T wave amplitudes during ventricular repolarization in the lead aVR (TAaVR) are shown to be associated with adverse cardiac events in patients with several cardiovascular diseases, such as postmyocardial infarction. However, the utility of TAaVR has not been previously evaluated in patients with cardiomyopathy who have received implantable cardioverter defibrillators (ICD). Patients with ischemic or nonischemic cardiomyopathy (ICM or NICM, respectively) and who received an ICD may experience worsening of their condition due to the introduction of electric shock during treatment. This study aimed to investigate the utility of TAaVR in the prediction of cardiac events in ICM or NICM patients with ICD.


JACC: Clinical Electrophysiology | 2016

Impact of Updated Diagnostic Criteria for Long QT Syndrome on Clinical Detection of Diseased Patients: Results From a Study of Patients Carrying Gene Mutations

Kenshi Hayashi; Tetsuo Konno; Noboru Fujino; Hideki Itoh; Yusuke Fujii; Yoko Imi-Hashida; Hayato Tada; Toyonobu Tsuda; Yoshihiro Tanaka; Takekatsu Saito; Hidekazu Ino; Masa-aki Kawashiri; Kunio Ohta; Minoru Horie; Masakazu Yamagishi

OBJECTIVESnIn this study, we scored patients with long QT syndrome (LQTS) according to the different Schwartz diagnostic criteria from 1993, 2006, and 2011, and to examine the validation of the criteria in relevance to the frequency of LQTS-related gene mutation.nnnBACKGROUNDnAlthough updated diagnostic criteria have been used in clinical settings, few data exist regarding their impact on the diagnosis of LQTS.nnnMETHODSnWe used a cohort of 132 patients who presented with prolonged QTc intervals and/or abnormal clinical history in cardiac screening and who underwent exercise stress testing. LQTS scores ofxa0≥3.5 points according to the 2006 and the 2011 criteria were considered to indicate a high probability of LQTS, as opposed to the 4 points used by the 1993xa0criteria. The 2011 criteria were updated by adding the evaluation of the recovery phase of exercise.nnnRESULTSnThe 2011 criteria significantly increased the number of high probability patients (nxa0= 62) compared with the 1993 criteria (nxa0= 32; pxa0= 0.0002) or the 2006 criteria (nxa0= 36; pxa0= 0.0014). The percentage of mutation carriers in those with an intermediate score, which was rather high using the 1993 (53%) and 2006 criteria (53%), was greatly reduced with the 2011 criteria (15%, pxa0= 0.0014 vs. the 1993 criteria, and pxa0= 0.0013 vs. the 2006 criteria). Among 54xa0mutation carriers, the 1993, the 2006, and the 2011 criteria identified a high probability of carriers in 25 patients (46%xa0sensitivity and 91% specificity), 27 patients (50% sensitivity and 88% specificity), and 48 patients (89% sensitivity and 82% specificity), respectively.nnnCONCLUSIONSnThe use of the 2011 criteria will facilitate the diagnosis of LQTS and will decrease the number of false negative results.

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