著者

Takeshi Yamashita Yukihiro Koretsune Yuejin Yang Shih-Ann Chen Namsik Chung Yuichi J. Shimada Tetsuya Kimura Koichi Miyazaki Kenji Abe Michele Mercuri Christian T. Ruff Robert P. Giugliano

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-15-1082, (Released:2016-02-16)

参考文献数

23

被引用文献数

13 75

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Background:In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia.Methods and Results:Patients aged ≥21 years with documented AF and CHADS score ≥2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0–3.0. Patients with a creatinine clearance of 30–50 ml/min, weighing ≤60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.35% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31–0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63–1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41–0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21–0.54, P<0.001).Conclusions:Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population.

著者

Stephen A. McCullough Michael A. Fifer Pouya Mohajer Patricia A. Lowry Caitlin O’Callaghan Reen Aaron L. Baggish Gus J. Vlahakes Yuichi J. Shimada

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-17-0959, (Released:2018-03-09)

参考文献数

25

被引用文献数

8

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Background:The clinical characteristics associated with elevated right atrial pressure (RAP) in hypertrophic cardiomyopathy (HCM) are unknown. Few data exist as to whether elevated RAP has prognostic implications in patients with HCM. This study investigated the clinical correlates and prognostic value of elevated RAP in HCM.Methods and Results:This retrospective cohort study was performed on 180 patients with HCM who underwent right heart catheterization between 1997 and 2014. Elevated RAP was defined as >8 mmHg. Baseline characteristics, mean pulmonary artery pressure, and mean pulmonary capillary wedge pressure (PCWP) were assessed for association with elevated RAP. The predictive value of elevated RAP for all-cause mortality and the development of atrial fibrillation (AF), ventricular tachycardia/fibrillation (VT/VF), and stroke was evaluated. Elevated RAP was associated with higher New York Heart Association class, dyspnea on exertion, orthopnea, edema, jugular venous distention, larger left atrial size, right ventricular hypertrophy, higher pulmonary artery pressure, and higher PCWP. RAP independently predicted all-cause mortality (adjusted hazard ratio [aHR] 2.18 per 5-mmHg increase, 95% confidence interval [CI] 1.05–4.50, P=0.04) and incident AF (aHR 1.85 per 5-mmHg increase, 95% CI 1.20–2.85, P=0.005). Elevated RAP did not predict VT/VF (P=0.36) or stroke (P=0.28).Conclusions:Elevated RAP in patients with HCM is associated with left-sided heart failure and is an independent predictor of all-cause mortality and new-onset AF.

著者

Lusha W. Liang Yuichi J. Shimada

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-21-0349, (Released:2021-06-08)

参考文献数

51

被引用文献数

3

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Endotyping is an emerging concept in which diseases are classified into distinct subtypes based on underlying molecular mechanisms. Heart failure (HF) is a complex clinical syndrome that encompasses multiple endotypes with differential risks of adverse events, and varying responses to treatment. Identifying these distinct endotypes requires molecular-level investigation involving multi-“omics” approaches, including genomics, transcriptomics, proteomics, and metabolomics. The derivation of these HF endotypes has important implications in promoting individualized treatment and facilitating more targeted selection of patients for clinical trials, as well as in potentially revealing new pathways of disease that may serve as therapeutic targets. One challenge in the integrated analysis of high-throughput omics and detailed clinical data is that it requires the ability to handle “big data”, a task for which machine learning is well suited. In particular, unsupervised machine learning has the ability to uncover novel endotypes of disease in an unbiased approach. In this review, we will discuss recent efforts to identify HF endotypes and cover approaches involving proteomics, transcriptomics, and genomics, with a focus on machine-learning methods.

著者

Sae X. Morita Yanling Zhao Kohei Hasegawa Michael A. Fifer Mathew S. Maurer Muredach P. Reilly Hiroo Takayama Yuichi J. Shimada

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.62, no.5, pp.1035-1041, 2021-09-29 (Released:2021-09-30)

参考文献数

32

被引用文献数

2

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Septal reduction therapy (SRT) -i.e. septal myectomy and alcohol septal ablation-has been performed to treat medically refractory hypertrophic cardiomyopathy (HCM) for decades. However, it is largely unknown whether SRT prevents HCM-related cardiovascular events or death. The objective was to examine the effects of SRT on acute cardiovascular events and all-cause mortality in HCM. We performed a propensity score (PS) -matched study using databases that capture all hospitalizations and outpatient visits in New York state. We identified patients with HCM who underwent SRT between 2007 and 2014 (i.e. the SRT group) and those who had never had SRT but had at least one hospitalization for HCM during the same period (i.e. the control group). We performed PS matching at a 1:1 ratio. The primary outcome was a composite of acute cardiovascular events and all-cause mortality during 0-180 days and 181-360 days. The secondary outcome was 180- and 360-day all-cause mortality. We included 846 patients with HCM (423 PS-matched pairs). Patients who underwent SRT had a lower risk of the primary outcome event (0-180 days: odds ratio [OR], 0.54; 95% confidence intervals (CI), 0.37-0.80; P = 0.002 and 181-360 days: OR, 0.33; 95% CI, 0.22-0.51; P < 0.0001). Furthermore, the risk of all-cause mortality was lower at 180 days (OR, 0.37; 95% CI, 0.22-0.63; P = 0.0003) and 360 days post-SRT (OR, 0.32; 95% CI, 0.20-0.51; P < 0.0001). In conclusion, our PS-matched study using population-based datasets demonstrated that SRT was associated with a reduced risk of a composite of acute cardiovascular events and all-cause mortality in HCM during the first post-SRT year.

著者

Takeshi Yamashita Yukihiro Koretsune Yuejin Yang Shih-Ann Chen Namsik Chung Yuichi J. Shimada Tetsuya Kimura Koichi Miyazaki Kenji Abe Michele Mercuri Christian T. Ruff Robert P. Giugliano

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.80, no.4, pp.860-869, 2016-03-25 (Released:2016-03-25)

参考文献数

23

被引用文献数

48 75

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Background:In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia.Methods and Results:Patients aged ≥21 years with documented AF and CHADS score ≥2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0–3.0. Patients with a creatinine clearance of 30–50 ml/min, weighing ≤60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.34% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31–0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63–1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41–0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21–0.54, P<0.001).Conclusions:Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population. (Circ J 2016; 80: 860–869)

著者

Yuichi J. Shimada Takeshi Yamashita Yukihiro Koretsune Tetsuya Kimura Kenji Abe Shunichi Sasaki Michele Mercuri Christian T. Ruff Robert P. Giugliano

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-15-0574, (Released:2015-10-09)

参考文献数

20

被引用文献数

6 31

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Background:In 21,105 patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial, edoxaban was non-inferior to warfarin in preventing thromboembolic events while reducing bleeding. We compared results in Japan with the rest of East Asia (EA), including China, Korea, and Taiwan.Methods and Results:We compared baseline characteristics, time-in-therapeutic range (TTR) for warfarin, and outcomes (efficacy: stroke or systemic embolic events [SEE], safety: major bleeding). Interaction P values were used to assess for effect modification of treatment (higher-dose edoxaban [HDE, 60 mg/30 mg] vs. warfarin; lower-dose edoxaban [LDE, 30 mg/15 mg] vs. warfarin) by region with adjustments for baseline characteristics. Fewer patients in Japan (n=1,010) were female, taking aspirin or amiodarone, naïve to warfarin (P<0.001 for each), had a history of stroke or transient ischemic attack (P=0.02), and more patients needed dose reduction (P<0.001) compared with EA (n=933). The mean TTR was higher in Japan (70% vs. 56%, P<0.001). Evidence for statistical interactions was observed for HDE vs. warfarin by region for stroke/SEE (adjusted P-int=0.052) and major bleeding (adjusted P-int=0.048) with greater relative efficacy and safety with HDE in EA compared with Japan. No interactions were observed for LDE vs. warfarin after adjustment.Conclusions:HDE had a greater relative efficacy and safety in EA compared with Japan that was only partially explained by differences in baseline characteristics and TTR.