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TOGI Kiyonori

    Kindai University Nara Hospital　Lecturer
Last Updated :2024/04/25

Researcher Information

Degree

  • M. D.（2004/05 Kyoto University）

J-Global ID

Research Areas

  • Life sciences / Cardiology

Published Papers

  • Yuta Tsujisaka; Yugo Yamashita; Takeshi Morimoto; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Jiro Sakamoto; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    Thrombosis research 232 35 - 42 2023/12 
    BACKGROUND: The RIETE score could be specifically useful for identification of low-risk pulmonary embolism (PE) patients for home treatment. However, the external validation of the RIETE score has been limited. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). The current study population consisted of 1479 patients with acute PE, who were divided into 2 groups; RIETE scores of 0 (N = 260) and ≥ 1 (N = 1219). RESULTS: The cumulative 10-day and 30-day incidences of a composite endpoint of all-cause death, recurrent PE, or major bleeding were lower in patients with the RIETE score of 0 than in those with the RIETE score of ≥1 (10-day: 0.4 % vs. 6.7 %, P < 0.001, and 30-day: 0.4 % vs. 10.0 %, P < 0.001). The area under the receiver-operating characteristic curve (AUC) in the RIETE score for the 10-day composite endpoint showed numerically better predictive ability than that in the sPESI score (0.77 vs. 0.73, P = 0.07), and the AUC in the RIETE score for the 30-day composite endpoint showed significantly better predictive ability than that in the sPESI score (0.77 vs. 0.71, P = 0.003). CONCLUSIONS: The RIETE score was well validated in the current large real-world registry. The RIETE score of 0 could identify patients with reasonably low risks of the 10-day and 30-day composite endpoint of all-cause death, recurrent PE, or major bleeding.
  • Kotaro Takahashi; Yugo Yamashita; Takeshi Morimoto; Tomohisa Tada; Hiroki Sakamoto; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Jiro Sakamoto; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    International journal of cardiology 383 89 - 95 2023/07 
    BACKGROUND: There is still a scarcity of data on the relation between age and long-term clinical outcomes of patients with venous thromboembolism (VTE). METHODS: The COMMAND VTE Registry was a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We divided the entire cohort into 3 groups: patients aged <65 years (N = 1100, 36.7%), patients aged 65 ≤ and ≤ 80 years (N = 1314, 43.4%), and patients aged >80 years (N = 603, 19.9%). RESULTS: Discontinuation of anticoagulation therapy during the follow-up period was most frequent in patients aged <65 years (44%, 38% and 33%, P < 0.001). The cumulative 5-year incidences were 12.7%, 9.8% and 7.4% for recurrent VTE, 10.8%, 12.2% and 14.9% for major bleeding, and 23.0%, 31.4%, and 38.6% for all-cause death. Adjusting for cofounders and taking into account the competing risk of all-cause death, the lower risk of patients aged >80 years, and those aged 65 ≤ and ≤ 80 years relative to those aged <65 years remained significant for recurrent VTE (65 ≤ age ≤ 80 years, HR: 0.71, 95%CI: 0.53-0.94, P = 0.02; age > 80 years, HR: 0.59, 95%CI: 0.39-0.89, P = 0.01), and the risk remained insignificant for major bleeding (65 ≤ age ≤ 80 years, HR: 1.00, 95%CI: 0.76-1.31, P = 0.98; age > 80 years, HR: 1.17, 95%CI: 0.83-1.65, P = 0.37). CONCLUSIONS: In the current real-world VTE registry, there was no significant difference in the risk of major bleeding depending on different age groups, while younger patients showed an excess risk for recurrent VTE compared with older patients.
  • Yugo Yamashita; Takeshi Morimoto; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Jiro Sakamoto; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    The American journal of cardiology 187 38 - 47 2023/01 
    Data on the impact of heart rate (HR) at diagnosis on clinical outcomes in patients with acute pulmonary embolism (PE) remain scarce. The present study population consisted of 1,532 patients with PE; the patients were divided into 4 groups, including (1) HR <80 beats/min (n = 451, 29%), (2) 80 ≤HR <100 beats/min (n = 620, 40%), (3) 100 ≤HR <110 beats/min (n = 215, 14%), and (4) HR ≥110 beats/min (n = 246, 16%). The cumulative 30-day incidences of all-cause death were significantly higher in the 100 ≤HR <110 and HR ≥110 beats/min groups than in the HR <80 beats/min group. Incidences were 2.7%, 3.6%, 6.6%, and 5.7% (p = 0.04) in the HR <80 beats/min, 80 ≤HR <100 beats/min, 100 ≤HR <110 beats/min, and HR ≥110 beats/min groups, respectively. With the HR <80 beats/min group as reference, the 100 ≤HR <110 and HR ≥110 groups, but not the 80 ≤HR <100 group, were significantly associated with an increased risk of 30-day all-cause death. Hazard ratio was 2.53 (95% confidence interval [CI] 1.17 to 5.56, p = 0.02) for the 80 ≤HR <100 beats/min group, 2.20 (95% CI 1.02 to 4.84, p = 0.046) for the 100 ≤HR <110 beats/min group, and 1.34 (95% CI 0.67 to 2.79, p = 0.41) for the HR ≥110 beats/min group. The cumulative 30-day incidences of all-cause death in patients with simplified Pulmonary Embolism Severity Index score = 0 were 0.6%, 0.3%, and 0.7% when based on cut-off values of HR ≥110 beats/min, HR ≥100 beats/min, and ≥80 beats/min, respectively. Patients with moderate tachycardia (100 ≤HR <110) seemed to be at comparable risk of 30-day all-cause death to those with HR ≥110 beats/min and at higher risk of 30-day all-cause death than those with HR <80 beats/min; this may suggest a potential benefit of the alternative cut-off value of HR ≥100 beats/min in the simplified Pulmonary Embolism Severity Index score for identification of low-risk patients.
  • Yugo Yamashita; Takeshi Morimoto; Kazushige Kadota; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Moriaki Inoko; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Jiro Sakamoto; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    Scientific reports 12 (1) 22437 - 22437 2022/12 
    There is a paucity of data on management strategies and clinical outcomes after recurrent venous thromboembolism (VTE). In a multicenter registry enrolling 3027 patients with acute symptomatic VTE, the current study population was divided into the following 3 groups: (1) First recurrent VTE during anticoagulation therapy (N = 110); (2) First recurrent VTE after discontinuation of anticoagulation therapy (N = 116); and (3) No recurrent VTE (N = 2801). Patients with first recurrent VTE during anticoagulation therapy more often had active cancer (45, 25 and 22%, P < 0.001). Among 110 patients with first recurrent VTE during anticoagulation therapy, 84 patients (76%) received warfarin at recurrent VTE with the median prothrombin time-international normalized ratio (PT-INR) value at recurrent VTE of 1.6, although patients with active cancer had a significantly higher median PT-INR value at recurrent VTE compared with those without active cancer (2.0 versus 1.4, P < 0.001). Within 90 days after recurrent VTE, 23 patients (20.9%) during anticoagulation therapy and 24 patients (20.7%) after discontinuation of anticoagulation therapy died. Active cancer was a major cause of recurrent VTE during anticoagulation therapy as a patient-related factor, while sub-optimal intensity of anticoagulation therapy was a major cause of recurrent VTE during anticoagulation therapy as a treatment-related factor, particularly in patients without active cancer.
  • Yugo Yamashita; Takeshi Morimoto; Kazushige Kadota; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Moriaki Inoko; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Jiro Sakamoto; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    Thrombosis research 219 30 - 39 2022/11 
    INTRODUCTION: There is still a scarcity of data on causes of long-term mortality in patients with venous thromboembolism (VTE). MATERIALS AND METHODS: The COMMAND VTE Registry is a physician-initiated, retrospective, multicenter cohort study in which consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan were included between January 2010 and August 2014. We investigated detailed causes and risk factors for long-term mortality. RESULTS: During a median observation period of 1218 days, a total of 764 patients died, and the prevalence of active cancer was higher in patients who died than in patients alive (61 % versus 10 %, P < 0.001). The cumulative incidences of cardiac death, pulmonary embolism (PE)-related death, bleeding death, cancer death, and non-cardiovascular non-cancer death were 2.2 %, 2.9 %, 2.0 %, 16.1 %, and 6.7 % at 5 years, respectively. The incidence of cancer death increased gradually, which was the most common cause of long-term death. Among patients without active cancer, the incidence of PE-related death increased rapidly and became a plateau beyond the acute phase, whereas the incidence of non-cardiovascular non-cancer death kept increasing, which became most common in the long term. The separate multivariable analysis among patient with and without active cancer identified independent risk factors of all-cause death including a few patient characteristics among patients with active cancer and several patient characteristics among patients without active cancer. CONCLUSIONS: Cancer was the most common cause of long-term mortality, while non-cardiovascular non-cancer death became most common among patients without active cancer.
  • Seiichi Hiramori; Yugo Yamashita; Takeshi Morimoto; Kazushige Kadota; Toru Takase; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Moriaki Inoko; Tomohisa Tada; Toshiaki Izumi; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Mitsuo Matsuda; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yoshihisa Nakagawa; Takao Kato; Koh Ono; Kenji Ando; Takeshi Kimura
    Journal of cardiology 80 (5) 487 - 494 2022/11 [Refereed]
     
    BACKGROUND: Vitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement >5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate. RESULTS: The group with TTR ≥70 % based on PT-INR range ≥1.5 and <2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28-0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p < 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked). CONCLUSIONS: The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and <2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes.
  • Yugo Yamashita; Takeshi Morimoto; Kazushige Kadota; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Moriaki Inoko; Tomohisa Tada; Toshiaki Izumi; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    International journal of cardiology 343 107 - 113 2021/11 
    BACKGROUND: There is a paucity of data on the long-term clinical outcomes according to the severity of pulmonary embolism (PE) at initial diagnosis. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE). After excluding 1312 patients without PE, the current study population consisted of 1715 patients with PE, who were divided into 3 groups according to the clinical severity; massive PE, sub-massive PE and low-risk PE. RESULTS: There were 179 patients (10%) with massive PE, 742 patients (43%) with sub-massive PE, and 794 patients (46%) with low-risk PE. By the landmark analysis at 3 months, the cumulative incidences of recurrent VTE were similar among the 3 groups both within and beyond 3 months (Massive PE: 2.9%, Sub-massive PE: 4.2%, and Low-risk PE: 3.3%, P = 0.61, and 4.3%, 8.8%, and 7.8% at 5 years, P = 0.47, respectively). After adjusting confounders, the risk of massive PE relative to low-risk PE for recurrent VTE beyond 3 months remained insignificant (adjusted HR 0.54, 95% CI: 0.13-1.51, P = 0.27). Patients with massive PE at initial diagnosis more often presented as severe recurrent PE events than those with sub-massive and low-risk PE. CONCLUSIONS: In the current real-world large registry, the long-term risk of overall recurrent VTE in patients with massive PE at initial diagnosis did not significantly differ from those with sub-massive and low-risk PE beyond 3 months, although patients with massive PE at initial diagnosis more frequently developed recurrent VTE as PE with severe clinical presentation.
  • Reo Hata; Yugo Yamashita; Takeshi Morimoto; Kazushige Kadota; Hidewo Amano; Ryosuke Murai; Kohei Osakada; Arata Sano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Kosuke Doi; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yuta Tsujisaka; Yuta Seko; Kazuki Matsushita; Fumiya Yoneda; Takao Kato; Koh Ono; Takeshi Kimura
    Journal of thrombosis and thrombolysis 53 (2) 540 - 549 2021/09 
    Anticoagulation therapy is prescribed for the prevention of recurrence in patients with venous thromboembolism, which could be temporarily interrupted during invasive procedures. The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We identified patients who underwent invasive procedures during the entire follow-up period and evaluated periprocedural managements and clinical outcomes at 30 days after invasive procedures. During a median follow-up period of 1213 (IQR: 847-1764) days, 518 patients underwent invasive procedures with the cumulative incidences of 5.8% at 3 months, 11.1% at 1 year, and 24.0% at 5 years. Among 382 patients in high bleeding-risk category of invasive procedures, anticoagulation therapy had been discontinued already in 62 patients (16%) and interrupted temporarily in 288 patients (75%) during the invasive procedures with bridging anticoagulation therapy with heparin in 214 patients (56%). Among 80 patients in low bleeding-risk category, anticoagulation therapy had been already discontinued in 15 patients (19%) and interrupted temporarily in 31 patients (39%) during invasive procedure with bridging anticoagulation therapy with heparin in 17 patients (21%). At 30 days after the invasive procedures, 14 patients (2.7%) experienced recurrent VTE, while 28 patients (5.4%) had major bleeding. This study elucidated the real-world features of peri-procedural management and prognosis in patients with VTE who underwent invasive procedures during follow-up in the large multicenter VTE registry. The 30-day incidence rates of recurrent VTE and major bleeding events were 2.7% and 5.4%.
  • Yugo Yamashita; Hidewo Amano; Takeshi Morimoto; Kazushige Kadota; Reo Hata; Kazuki Matsushita; Kohei Osakada; Arata Sano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Moriaki Inoko; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Takao Kato; Koh Ono; Takeshi Kimura
    Journal of thrombosis and thrombolysis 2021/07 
    Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Yusuke Morita; Tomohisa Tada; Toshiaki Izumi; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Journal of thrombosis and thrombolysis 51 (3) 779 - 788 2021/04 
    There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P < 0.001), and with more severe hemodynamic condition for PE patients. The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the two groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P = 0.87), as well as among DVT patients (0.0% vs. 1.5%, P = 0.24). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30-day were not significantly different between the 2 groups among PE patients, nor among DVT only patients. In conclusion, the VTE patients diagnosed on weekends presented more often with PE, and with more severe condition for PE patients. Nevertheless, the risk for 30-day mortality was not significantly different between patients diagnosed on weekends and on weekdays.
  • Shushi Nishiwaki; Yusuke Morita; Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Moriaki Inoko; Takeshi Kimura
    Journal of cardiology 77 (4) 395 - 403 2021/04 
    BACKGROUND: The majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE. METHODS: The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status. RESULTS: There were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively). CONCLUSIONS: Acute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT.
  • Kazuhisa Kaneda; Yugo Yamashita; Takeshi Morimoto; Hideo Amano; Toru Takase; Seiich Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Yusuke Morita; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yoshihisa Nakagawa; Yuji Nishimoto; Syunsuke Saga; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Katsuhisa Ishii; Hiroshi Mabuchi; Kensuke Takabayashi; Shun Hojo; Tetsuma Kawaji; Akihiro Kushiyama; Hidenori Yaku; Kenji Nakatsuma; Masashi Kato; Takafumi Yokomatsu; Shinji Miki; Takeshi Kimura
    Thrombosis research 198 26 - 33 2021/02 
    INTRODUCTION: There is a paucity of data on the influence of low body weight on clinical outcomes in patients with acute venous thromboembolism (VTE). MATERIALS AND METHODS: The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2778 patients with available body weight value, who were divided into 2 groups; 1705 patients with lower body weight (≤60 kg) and 1073 patients with higher body weight (>60 kg). RESULTS: Patients with lower body weight were older (70.8 versus 60.9 years, P < 0.001), and more often women (75% versus 38%, P < 0.001), and more often had active cancer (27% versus 19%, P < 0.001) than those with higher body weight. The cumulative 5-year incidence of recurrent VTE was not significantly different between the 2 groups (10.6% versus 10.7%, P = 0.51). The cumulative 5-year incidences of major bleeding and all-cause death were significantly higher in patients with lower body weight than in those with higher body weight (14.6% versus 9.6%, P < 0.001, and 35.8% versus 19.8%, P < 0.001, respectively). The excess adjusted risk of patients with lower body weight relative to those with higher body weight remained significant for major bleeding and all-cause death (HR 1.57, 95%CI: 1.16-2.12, P = 0.003, and HR 1.50, 95%CI: 1.24-1.81, P < 0.001, respectively). CONCLUSIONS: In the current Japanese real-world registry, there were a high proportion of patients with low body weight, who had a higher risk for major bleeding and mortality without significant excess risk for recurrent VTE.
  • Yuji Nishimoto; Yugo Yamashita; Kitae Kim; Takeshi Morimoto; Syunsuke Saga; Hidewo Amano; Toru Takase; Seiichi Hiramori; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yukihito Sato; Takeshi Kimura
    Circulation journal : official journal of the Japanese Circulation Society 84 (11) 2006 - 2014 2020/10 
    BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06-3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04-3.04, P=0.037) were independently associated with an increased risk of major bleeding. CONCLUSIONS: Major bleeding events were common during anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding.
  • Yuji Nishimoto; Yugo Yamashita; Takeshi Morimoto; Syunsuke Saga; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yukihito Sato; Takeshi Kimura
    Thrombosis research 191 66 - 75 2020/07 
    INTRODUCTION: The external validation of the modified Ottawa score to predict the risk of recurrence in patients with cancer-associated venous thromboembolism (VTE) has not yet been firmly established. The present study aimed to evaluate the utility and limitations of the modified Ottawa score in the risk stratification of recurrent VTE in patients with cancer-associated VTE. MATERIALS AND METHODS: The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 614 cancer-associated VTE patients, who were divided into 3 groups; High-risk group: 202 patients (33%) with a modified Ottawa score ≥ 1, Intermediate-risk group: 269 patients (44%) with a score = 0, and Low-risk group: 143 patients (23%) with a score ≤ -1. RESULTS: Recurrent VTE occurred in 39 patients on anticoagulation therapy within 6 months. The cumulative incidence of recurrent VTE substantially increased in the higher risk categories by the modified Ottawa score (high-risk group: 13.6% [95%CI, 8.9%-20.2%], intermediate-risk group: 5.9% [95%CI, 3.5%-9.8%], and low-risk group: 3.0% [95%CI, 1.1%-7.8%], P = .02). The discriminating power of the score was modest with a C-statistic of 0.63. Each score component of the score had a different impact on recurrent events with a variable effect size. CONCLUSIONS: The risks of recurrence in patients with cancer-associated VTE substantially increased in the higher risk categories by using the modified Ottawa score, but the discriminating power of the score for recurrence was modest with a variable impact of each score component on recurrent events.
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Yuji Nishimoto; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Chest 157 (3) 636 - 644 0012-3692 2020/03 [Refereed]
     
    © 2019 American College of Chest Physicians Background: The simplified Pulmonary Embolism Severity Index (sPESI) score is a practical score for identification of patients with low-risk pulmonary embolism (PE), although it has not been applied in patients with active cancer. The current study aimed to evaluate the usefulness of the sPESI score in patients with PE and active cancer. Methods: The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic VTE. The current study population consisted of 368 patients with PE and active cancer. The 30-day clinical outcomes were compared between patients with sPESI score = 1 and patients with sPESI scores ≥ 2. Results: Overall, 37 patients (10%) died during the 30 days after diagnosis. The cumulative 30-day incidences of mortality, and PE-related death, were lower in patients with sPESI score = 1 than in patients with sPESI scores ≥ 2 (6.3% vs 13.1%; log-rank P =.03; and 0.7% vs 3.9%; log-rank P =.046). Among patients with sPESI score = 1, the predominant cause of death was cancer. There were no significant differences in the cumulative 30-day incidence of recurrent VTE and major bleeding between the two groups (3.9% vs 5.6%; log-rank P =.46; and 6.4% vs 4.5%; log-rank P =.45). Conclusions: Among patients with PE and active cancer, patients with sPESI score = 1 had a lower 30-day mortality rate compared with patients with sPESI scores ≥ 2, and they showed very low PE-related mortality risk, although the overall mortality rate remained high because of cancer-related mortality. They also showed relatively high risks for recurrence and major bleeding, suggesting the need for careful follow-up. Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000021132; URL: http://www.umin.ac.jp/ctr/index.htm
  • Yuji Nishimoto; Yugo Yamashita; Takeshi Morimoto; Syunsuke Saga; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yukihito Sato; Takeshi Kimura; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi
    Journal of Thrombosis and Haemostasis 18 (3) 624 - 632 1538-7933 2020/03 [Refereed]
     
    © 2019 International Society on Thrombosis and Haemostasis Background: The recently proposed VTE-BLEED score to predict the risk of major bleeding in patients with venous thromboembolisms (VTEs) on prolonged anticoagulation therapy was validated externally in randomized controlled trials and in a selected cohort, but not applied in non-selective cohorts. Objectives: The present study aimed to evaluate the generalizability of the VTE-BLEED score in a non-selective cohort. Patients/Methods: The COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic VTEs among 29 centers in Japan. The present study population consisted of 2124 patients with prolonged anticoagulation therapy beyond 30 days, including 2008 (95%) patients with a first VTE episode and 1075 (51%) with unprovoked VTEs, who were divided into 1445 patients (68%) with a VTE-BLEED score of ≥2 (high-risk group) and 679 (32%) with a VTE-BLEED score of <2 (low-risk group). Results: During a median follow-up period of 672 days, major bleeding events occurred in 121 patients. The cumulative 5-year incidence of major bleeding beyond 30 days was significantly higher in the high-risk group than low-risk group (13.2% versus 5.4%, P <.001). The hazard function curves demonstrated that the hazards of the high-risk group were consistently higher over time compared with the low-risk group, which suggested the long-term predictive ability of the score. Conclusions: In the present real-world VTE registry, the VTE-BLEED score had a long-term predictive ability for high-risk patients with major bleeding during prolonged anticoagulation therapy, which could be useful in determining the optimal duration of anticoagulation therapy in individual patients.
  • Yusuke Yoshikawa; Yugo Yamashita; Takeshi Morimoto; Hiroshi Mabuchi; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Tomoyuki Murakami; Takeshi Kimura
    The American journal of cardiology 125 (2) 189 - 197 0002-9149 2020/01 [Refereed]
     
    Statins, which are considered as essential for primary and secondary prevention of atherosclerotic diseases, were also reported to reduce first venous thromboembolism (VTE). However, the effect of statins on VTE recurrence remains conflicting. We aimed to examine the association between statin use and VTE recurrence in a large observational study in Japan. The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE in 29 centers in Japan between January 2010 and August 2014. In the current study, the entire cohort was divided into statin group (N = 437) and no-statin group (N = 2590) according to the status of statin use at baseline. The statin group as compared with the no-statin group was older (statin group 71.2 vs no-statin group 66.5 years, p <0.001), included more women (67% vs 60%, p = 0.008), and less frequently had active cancer (12% vs 25%, p <0.001). There was no significant difference in the clinical presentation of VTE (pulmonary embolism, 58% vs 56%, p = 0.44). The cumulative 3-year incidence of recurrent VTE was significantly lower in the statin group than the no-statin group (3.8% vs 8.8%, p <0.001). After adjusting for confounders including active cancer, statin use was associated with significantly lower risk for recurrent VTE (Hazard ratio 0.49, 95% confidence interval 0.29 to 0.78, p = 0.002). The results were consistent in a sensitivity sub-group analysis with and without active cancer. In conclusion, statin use was associated with significantly lower risk for the recurrent VTE in patients with VTE.
  • Yugo Yamashita; Koichiro Murata; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Ryuzo Nawada; Tomoya Onodera; Takeshi Kimura
    Thrombosis research 184 50 - 57 0049-3848 2019/12 [Refereed]
     
    INTRODUCTION: Pulmonary embolism (PE) and deep vein thrombosis (DVT) can be considered as one clinical entity, venous thromboembolism (VTE). However, the potential differences between PE and DVT might have to be taken into consideration for the decision-making of the optimal treatment strategies. MATERIALS AND METHODS: The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 1715 PE patients with or without DVT and 1312 DVT only patients. RESULTS: The adjusted risk for recurrent VTE was not significantly different between the PE and DVT only groups (HR 1.22, 95%CI 0.93-1.60, P = 0.15). PE patients developed recurrent VTE events more often as PE than as DVT only (62% and 38%). The adjusted excess mortality risk of PE patients relative to DVT only patients was significant (HR 1.29, 95%CI 1.11-1.50, P < 0.001), with markedly higher cumulative 30-day incidence of all-cause death in PE patients (6.4% and 1.4%, P < 0.001). The most frequent cause of deaths was cancer death in both groups, and second most frequent cause of deaths in PE patients was fatal PE, most of which developed within 30 days. CONCLUSIONS: The risk for recurrent VTE was not significantly different between PE and DVT, although PE was more likely to develop recurrent VTE as PE. The mortality risk of PE seemed to be higher than that of DVT, which was more remarkable in the short term due to PE death, and less remarkable in the long term due to cancer death.
  • Yuji Nishimoto; Yugo Yamashita; Takeshi Morimoto; Syunsuke Saga; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yukihito Sato; Takeshi Kimura
    Journal of thrombosis and thrombolysis 48 (4) 587 - 595 0929-5305 2019/11 [Refereed]
     
    There is still uncertainty about the optimal usage of thrombolysis for acute pulmonary embolisms (PEs), leading to a widely varying usage in the real world. The COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan. The present study population consisted of 1549 patients with PEs treated with tissue plasminogen activator (t-PA) thrombolysis (N = 180, 12%) or without thrombolysis (N = 1369). Thrombolysis with t-PA was implemented in 33% of patients with severe PEs, and 9.2% of patients with mild PEs with a wide variation across the participating centers. Patients with t-PA thrombolysis were younger, and less frequently had active cancer, history of major bleeding, and anemia. At 30 days, t-PA thrombolysis as compared to no thrombolysis was associated with similar mortality rates (5.0% vs. 6.9%, P = 0.33), but a lower adjusted mortality risk (OR 0.41; 95% CI 0.18-0.90, P = 0.03), while it was associated with a trend for higher rates of major bleeding (5.6% vs. 2.9%, P = 0.06) and a significantly higher adjusted risk for major bleeding (OR 2.39; 95% CI 1.06-5.36, P = 0.03). In patients with severe PEs, the mortality rates at 30 days were significantly lower in the t-PA thrombolysis group than no thrombolysis group (15% vs. 37%, P = 0.006). In the present real-world VTE registry in Japan, t-PA thrombolysis was not infrequently implemented, not only in patients with severe PEs, but also in patients with mild PEs. A substantial mortality risk reduction might be suggested with t-PA thrombolysis in patients with severe PEs.
  • Jiro Sakamoto; Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Toshihiro Tamura; Yoshihisa Nakagawa; Takeshi Kimura
    Circulation journal : official journal of the Japanese Circulation Society 83 (11) 2271 - 2281 1346-9843 2019/10 [Refereed]
     
    BACKGROUND: There is a paucity of data on the management and prognosis of cancer-associated venous thromboembolism (VTE), leading to uncertainty about optimal management strategies.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients in Japan between 2010 and 2014. We divided the entire cohort into 3 groups: active cancer (n=695, 23%), history of cancer (n=243, 8%), and no history of cancer (n=2089, 69%). The rate of anticoagulation discontinuation was higher in patients with active cancer (43.5%, 27.0%, and 27.0%, respectively, at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding, and all-cause death were higher in patients with active cancer (recurrent VTE: 17.7%, 10.2%, and 8.6%, P<0.001; major bleeding: 26.6%, 8.8%, and 9.3%, P<0.001; all-cause death: 73.1%, 28.6%, 14.6%, P<0.001). Among the 4 groups classified according to active cancer status, the cumulative 1-year incidence of recurrent VTE was higher in the metastasis group (terminal stage group: 6.4%, metastasis group: 22.1%, under chemotherapy group: 10.8%, and other group: 5.8%, P<0.001). CONCLUSIONS: In a current real-world VTE registry, patients with active cancer had higher risk for VTE recurrence, bleeding, and death, with variations according to cancer status, than patients without active cancer. Anticoagulation therapy was frequently discontinued prematurely in patients with active cancer in discordance with current guideline recommendations.
  • Yugo Yamashita; Yusuke Yoshikawa; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    International journal of cardiology 292 198 - 204 0167-5273 2019/10 [Refereed]
     
    BACKGROUND: The duration of anticoagulation therapy after venous thromboembolism (VTE) should be based on the balance between risks of recurrent VTE and bleeding. However, there is uncertainty about the impact of these events on subsequent mortality. METHODS: We evaluated the association of recurrent VTE and major bleeding events with mortality among 3026 patients in the COMMAND VTE Registry. We estimated the risks of the recurrent VTE events and the major bleeding events for subsequent mortality by the time-updated multivariable Cox proportional hazard model. RESULTS: During the median follow-up period of 1218 days, 225 patients developed recurrent VTE events, 274 patients developed major bleeding events, and 763 patients died. The multivariable Cox proportional hazard model revealed that both the recurrent VTE and major bleeding events were strongly associated with subsequent mortality risk (recurrent VTE: HR 3.24, 95%CI 2.57-4.08, P < 0.001; major bleeding: HR 3.53, 95%CI 2.88-4.31, P < 0.001). Both the recurrent pulmonary embolism (PE) and recurrent deep vein thrombosis (DVT) events were associated with subsequent mortality risk (recurrent PE events: HR 4.42, 95%CI 3.28-5.95, P < 0.001; recurrent DVT events: HR 2.42, 95%CI 1.75-3.36, P < 0.001). CONCLUSIONS: In the real-world patients with VTE, both the recurrent VTE events and the major bleeding events were strongly associated with subsequent mortality risk with the comparable effect size. The recurrent PE and recurrent DVT events were also associated with increased risks for mortality, although the magnitude of the effect on mortality was numerically greater with the recurrent PE events than with the recurrent DVT events.
  • Maki Oi; Yugo Yamashita; Mamoru Toyofuku; Takeshi Morimoto; Yasuyo Motohashi; Takashi Tamura; Kazuaki Kaitani; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Masaharu Akao; Yohei Kobayashi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Journal of thrombosis and thrombolysis 49 (4) 551 - 561 0929-5305 2019/09 [Refereed]
     
    The relationship between D-dimer level at diagnosis and long-term clinical outcomes has not been fully evaluated in venous thromboembolism (VTE). The COMMAND VTE Registry is a multicenter registry enrolling consecutive acute symptomatic VTE patients in Japan. Patients with available D-dimer levels at diagnosis (N = 2852) were divided into 4 groups according to the D-dimer levels; Quartile 1 (0.0-4.9 µg/mL): N = 682, Quartile 2 (5.0-9.9 µg/mL) N = 694, Quartile 3 (10.0-19.9 µg/mL) N = 710, and Quartile 4 (≥ 20.0 µg/mL): N = 766. The cumulative incidence of all-cause death was higher in Quartile 4 throughout the entire follow-up period (19.9%, 24.9%, 28.8%, and 41.5% at 5-year, P < 0.0001), as well as both within and beyond 30-day. After adjustment, the excess risk of Quartile 4 relative to Quartile 1 for all-cause death remained significant (HR 1.60, 95% CI 1.29-2.03). Similarly, the excess risk of Quartile 4 relative to Quartile 1 for recurrent VTE was significant (HR 1.57, 95% CI 1.02-2.41), which was more prominent in the cancer subgroup. The dominant causes of death in Quartile 4 were pulmonary embolism within 30-day, and cancer beyond 30-day. In conclusions, in VTE patients, elevated D-dimer levels at diagnosis were associated with the increased risk for both short-term and long-term mortality. The higher mortality risk of patients with highest D-dimer levels was driven by the higher risk for fatal PE within 30-day, and by the higher risk for cancer death beyond 30-day. Elevated D-dimer levels were also associated with the increased risk for long-term recurrent VTE, which was more prominent in patients with active cancer.
  • Kitae Kim; Yugo Yamashita; Takeshi Morimoto; Takeshi Kitai; Takafumi Yamane; Natsuhiko Ehara; Makoto Kinoshita; Shuichiro Kaji; Hidewo Amano; Toru Takase; Seiichi Hiramori; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yutaka Furukawa; Takeshi Kimura
    Thrombosis and haemostasis 119 (9) 1498 - 1507 0340-6245 2019/09 [Refereed]
     
    BACKGROUND:  There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients. PATIENTS AND METHODS:  The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153). RESULTS:  During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23-4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51-3.59), anemia (HR, 1.75, 95% CI, 1.27-2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27-3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22-2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model. CONCLUSION:  Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.
  • Yuji Nishimoto; Yugo Yamashita; Takeshi Morimoto; Syunsuke Saga; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yukihito Sato; Takeshi Kimura
    Circulation journal : official journal of the Japanese Circulation Society 83 (6) 1377 - 1384 1346-9843 2019/05 [Refereed]
     
    BACKGROUND: Differences in the clinical characteristics and outcomes of venous thromboembolisms (VTEs) based on different clinical situations surrounding the onset might be important for directing appropriate treatment strategies, but have not yet been appropriately evaluated. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTEs in Japan between January 2010 and August 2014. We divided the study population into 3 groups: Out-of-hospital onset (n=2,308), In-hospital onset with recent surgery (n=310), and In-hospital onset without recent surgery (n=374). Active cancer was most prevalent in the In-hospital onset without recent surgery group, and least in the Out-of-hospital onset group (Out-of-hospital onset group: 20%, In-hospital onset with recent surgery group: 26%, and In-hospital onset without recent surgery group: 38%, P<0.001). The cumulative 5-year incidence of recurrent VTEs did not significantly differ across the 3 groups (11.4%, 5.8%, and 8.7%, respectively; P=0.11). The cumulative 5-year incidences of major bleeding and all-cause death were highest in the In-hospital onset without recent surgery group (11.1%, 8.5%, and 23.3%, P<0.001; 26.8%, 24.9%, and 48.4%, P<0.001, respectively). CONCLUSIONS: In the real-world VTE registry, the clinical characteristics and long-term outcomes substantially differed according to the clinical situation of VTE onset, suggesting the need for different treatment strategies for VTEs in different clinical settings.
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Yuji Nishimoto; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Yusuke Yoshikawa; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Thrombosis Research 177 1 - 9 0049-3848 2019/05 [Refereed]
     
    © 2019 Introduction: There is a paucity of data on patients with deep vein thrombosis (DVT) in upper extremities. Materials and methods: The COMMAND VTE Registry is a retrospective multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population included 2498 patients with upper or lower extremities DVT. Results: There were 74 patients (3.0%) with upper extremities DVT and 2424 patients with lower extremities DVT. Patients with upper extremities DVT more often had active cancer (58%) and central venous catheter use (22%). The proportion of concomitant pulmonary embolism at diagnosis was lower in patients with upper extremities DVT than in those with lower extremities DVT (14% and 51%, P < 0.001). Discontinuation of anticoagulation therapy was more frequent in patients with upper extremities DVT (63.8% and 29.8% at 1-year, P < 0.001). The cumulative 3-year incidence of recurrent VTE was not different between the 2 groups (9.8% and 7.4%, P = 0.43). After adjusting confounders, the risks of upper extremities DVT relative to lower extremities DVT for recurrent VTE remained insignificant (HR 0.94, 95%CI 0.36–2.01, P = 0.89). Conclusions: The prevalence of patients with DVT in upper extremities was 3.0% in the current large-scale real-world registry. Patients with DVT in upper extremities more often had active cancer at diagnosis and central venous catheter use as a transient risk factor for VTE, and less often had concomitant PE. Patients with DVT in upper extremities had similar long-term risk for recurrent VTE as those with DVT in lower extremities despite shorter duration of anticoagulation.
  • Yuji Nishimoto; Yugo Yamashita; Takeshi Morimoto; Syunsuke Saga; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Yukihito Sato; Takeshi Kimura
    Heart and vessels 34 (4) 669 - 677 0910-8327 2019/04 [Refereed]
     
    Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis (DVT). Identifying high-risk patients for the development of PTS might be useful for its prevention. The COMMAND VTE Registry is a multicenter registry that enrolled 3027 consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan between January 2010 and August 2014. The current study population consisted of 1298 patients with lower extremities DVTs who completed 3-year follow-up for those who developed PTS and those without PTS. We investigated risk factors for the development of PTS at the time of DVT diagnosis, using a multivariable logistic regression analysis. Of the entire 1298 study patients, 169 (13%) patients were diagnosed with PTS within 3 years. The rate for anticoagulation discontinuation during follow-up was not significantly different between those with and without PTS. Chronic kidney disease (OR 2.21, 95% CI 1.45-3.39, P < 0.001), leg swelling (OR 4.15, 95% CI 2.25-7.66, P < 0.001), absence of transient risk factors for VTEs (OR 2.39, 95% CI 1.55-3.67, P < 0.001), active cancer (OR 3.66, 95% CI 2.30-5.84, P < 0.001), and thrombophilia (OR 2.07, 95% CI 1.06-4.04, P = 0.03) were independent risk factors for the development of PTS. In this real-world Japanese DVT registry, we could identify several important risk factors for the development of PTS at the time of DVT diagnosis.
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Journal of thrombosis and thrombolysis 47 (3) 444 - 453 0929-5305 2019/04 [Refereed]
     
    The influence of anemia on the long-term clinical outcomes has not been fully evaluated in patients with venous thromboembolism (VTE). We evaluated the influence of anemia among 3012 patients in the COMMAND VTE Registry with a median follow-up period of 1219 days. The outcomes measures were ISTH major bleeding, recurrent VTE and all-cause death. There were 1012 patients (34%) with moderate/severe anemia (Hb ≤ 10.9 g/dl), 615 patients (20%) with mild anemia (Hb 11.0-12.9 g/dl for men, and 11.0-11.9 g/dl for women), and 1385 patients (46%) without anemia. The cumulative 5-year incidence of major bleeding was significantly higher in patients with anemia (moderate/severe anemia: 17.6%, mild anemia: 12.1%, and no anemia: 8.7%, P < 0.001). After adjusting the confounders, the excess risk of mild and moderate/severe anemia, respectively, relative to no anemia for major bleeding remained significant (mild: adjusted HR 1.41: [95% CI 1.00-1.98], P = 0.048; moderate/severe: adjusted HR 1.91: [95% CI 1.42-2.58], P < 0.001, respectively). The excess risk of moderate/severe anemia relative to no anemia was also significant for mortality (adjusted HR 2.89: 95% CI 2.45-3.42, P < 0.001), but the risk was neutral for recurrent VTE (adjusted HR 1.05: 95% CI 0.76-1.45, P = 0.77). In conclusions, VTE patients with mild and moderate/severe anemia had higher risk for major bleeding events without significant excess risk for recurrent VTE events, and the risk for major bleeding events increased according to the severity of anemia. We should pay more attention to the optimal intensity and duration of anticoagulation in VTE patients with anemia.
  • 日本における下大静脈フィルターの使用の現状 COMMAND VTEレジストリからの報告(Current Use of Inferior Vena Cava Filters in Japan: Reports from the COMMAND VTE Registry)
    高瀬 徹; 岩永 善高; 山下 侑吾; 藤田 晃輔; 渡邉 平太郎; 山治 憲司; 安岡 良文; 上野 雅史; 小夫家 和宏; 天野 秀生; 平森 誠一; 金 基泰; 東儀 圭則; 木村 剛; 宮崎 俊一
    日本循環器学会学術集会抄録集 (一社)日本循環器学会 83回 OJ01 - 8 2019/03
  • Yusuke Yoshikawa; Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Circulation Journal 83 (7) 1581 - 1589 1346-9843 2019 [Refereed]
     
    © 2019, Japanese Circulation Society. All rights reserved. Background: It remains controversial whether sex category is a risk for recurrent venous thromboembolism (VTE) and major bleeding among VTE patients. Methods and Results: The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients from 29 centers in Japan between January 2010 and August 2014. We compared the clinical characteristics and outcomes of men and women. Men accounted for 1,169 (39%) and women 1,858 (61%). Compared with women, men were younger (64.9±14.7 vs. 68.6±15.6 years old, P<0.001), more often had prior VTE (7.2% vs. 5.1%, P=0.02), and less often had transient risk factors for VTE (30% vs. 40%, P<0.001). The proportions of active cancer and pulmonary embolism were comparable between men and women (24% vs. 22%, P=0.26; 56% vs. 57%, P=0.48, respectively). The cumulative 3-year incidences of recurrent VTE, major bleeding, and all-cause death were not significantly different between men and women (7.0% vs. 8.6%, P=0.47; 10.6% vs. 9.2%, P=0.25; 25.2% vs. 23.4%, P=0.35, respectively). The adjusted risks of men relative to women for recurrent VTE and for major bleeding remained insignificant (HR 0.83, 95% CI 0.63–1.09, P=0.17; HR 1.15, 95% CI 0.90–1.47, P=0.25, respectively). Conclusions: In real-world VTE patients, the clinical characteristics differed between men and women, but there was not a large sex-related difference in the risks for recurrent VTE or major bleeding.
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hirotoshi Watanabe; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    The American journal of cardiology 122 (12) 2131 - 2141 0002-9149 2018/12 [Refereed]
     
    The influence of thrombocytopenia on the long-term clinical outcomes has not been thoroughly evaluated in patients with venous thromboembolism (VTE). This study sought to elucidate association of baseline thrombocytopenia with bleeding, recurrent VTE, and mortality risk. We evaluated the influence of baseline thrombocytopenia among 3,012 patients whose baseline platelet counts were available in the COMMAND VTE Registry in Japan with a median follow-up period of 1,219 days. Baseline thrombocytopenia was classified as follows: mild: 100,000 to 150,000/μl; moderate: 50,000 to 99,999/μl; and severe: <50,000/μl. The primary outcome measurement was International Society of Thrombosis and Hemostasis major bleeding, and the secondary outcome measurements were recurrent VTE and all-cause death. There were 167 patients (5.5%) with moderate or severe thrombocytopenia (moderate: 144 patients and severe: 23 patients), 523 patients (17.4%) with mild thrombocytopenia, and 2,322 patients (77.1%) without thrombocytopenia. The cumulative 5-year incidence of major bleeding was markedly higher in patients with moderate or severe thrombocytopenia (moderate or severe 29.4% vs mild: 14.1% vs no thrombocytopenia: 10.6%, p <0.001). After adjusting the confounders, the risk of or thrombocytopenia relative to no thrombocytopenia for major bleeding remained significant (adjusted hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.43 to 3.13, p <0.001). The excess risk of moderate or severe thrombocytopenia relative to no thrombocytopenia was also significant for mortality (adjusted HR 1.54, 95% CI 1.18 to 1.97, p = 0.002), but the risk was neutral for recurrent VTE (adjusted HR 1.05, 95% CI 0.55 to 1.81, p = 0.87). In conclusion, VTE patients with baseline moderate or severe thrombocytopenia had higher risk for major bleeding events and mortality without significant excess risk for recurrent VTE events.
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Maki Oi; Masaharu Akao; Yohei Kobayashi; Mamoru Toyofuku; Toshiaki Izumi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Minako Kinoshita; Kiyonori Togi; Hiroshi Mabuchi; Kensuke Takabayashi; Hiroki Shiomi; Takao Kato; Takeru Makiyama; Koh Ono; Takeshi Kimura
    European heart journal. Acute cardiovascular care 9 (4) 2048872618799993 - 2048872618799993 2048-8726 2018/09 [Refereed]
     
    BACKGROUND: The simplified pulmonary embolism severity index (sPESI) score has been reported to be useful in predicting 30-day mortality for patients with pulmonary embolism, which helps the identification of low-risk patients for early hospital discharge or home treatment. However, therapeutic decision-making should also be based on the risks of adverse events other than mortality. METHODS: The COMMAND VTE Registry is a multicentre registry enrolling consecutive patients with acute symptomatic venous thromboembolism in Japan between January 2010 and August 2014, and the current study population consisted of 1715 patients with pulmonary embolism. We calculated the sPESI score for each patient, and compared 30-day rates of mortality, recurrent venous thromboembolism and major bleeding between sPESI scores of 0 and 1 or greater. RESULTS: Patients with a sPESI score of 0 accounted for 383 (22%) patients, and 110 (6.4%) patients died within 30 days. The cumulative 30-day incidence of mortality was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (0.5% vs. 8.1%, log rank P<0.001). There was no significant difference in the cumulative 30-day incidence of recurrent venous thromboembolism between patients with a sPESI score of 0 and 1 or greater (1.3% vs. 2.8%, log rank P=0.11). The cumulative 30-day incidence of major bleeding was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (1.1% vs. 4.0%, log rank P=0.005). CONCLUSIONS: In patients with a sPESI score of 0, the 30-day mortality, recurrent venous thromboembolism and major bleeding rates were reasonably low. The sPESI score could be useful to identify candidates for early hospital discharge or home treatment.
  • YOKOTA Ryoji; NISHI Yuko; SUGITANI Yuuki; TAMADA Hiroyuki; OHI Yohei; ISHIKAWA Chisato; OHE Kentarou; UEMORI Noritsugu; MITSUOKA Hirokazu; TOGI Kiyonori; SHIROTANI Manabu
    Acta Medica Kindai University 43 (1) 35 - 42 0386-6092 2018/06 [Refereed]
  • Yugo Yamashita; Takeshi Morimoto; Hidewo Amano; Toru Takase; Seiichi Hiramori; Kitae Kim; Takashi Konishi; Masaharu Akao; Yohei Kobayashi; Takeshi Inoue; Maki Oi; Toshiaki Izumi; Kotaro Takahashi; Tomohisa Tada; Po-Min Chen; Koichiro Murata; Yoshiaki Tsuyuki; Hiroshi Sakai; Syunsuke Saga; Tomoki Sasa; Jiro Sakamoto; Chinatsu Yamada; Minako Kinoshita; Kiyonori Togi; Tomoyuki Ikeda; Katsuhisa Ishii; Kazuhisa Kaneda; Hiroshi Mabuchi; Hideo Otani; Kensuke Takabayashi; Mamoru Takahashi; Hiroki Shiomi; Takeru Makiyama; Koh Ono; Takeshi Kimura
    Circulation journal : official journal of the Japanese Circulation Society 82 (5) 1262 - 1270 1346-9843 2018/04 [Refereed]
     
    BACKGROUND: Venous thromboembolism (VTE) has a long-term risk of recurrence, which can be prevented by anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE between January 2010 and August 2014. The entire cohort was divided into the transient risk (n=855, 28%), unprovoked (n=1,477, 49%), and cancer groups (n=695, 23%). The rate of anticoagulation discontinuation was highest in the cancer group (transient risk: 37.3% vs. unprovoked: 21.4% vs. cancer: 43.5% at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding and all-cause death were highest in the cancer group (recurrent VTE: 7.9% vs. 9.3% vs. 17.7%, P<0.001; major bleeding: 9.0% vs. 9.4% vs. 26.6%, P<0.001; and all-cause death: 17.4% vs. 15.3% vs. 73.1%, P<0.001). After discontinuation of anticoagulation therapy, the cumulative 3-year incidence of recurrent VTE was lowest in the transient risk group (transient risk: 6.1% vs. unprovoked: 15.3% vs. cancer: 13.2%, P=0.001). The cumulative 3-year incidence of recurrent VTE beyond 1 year was lower in patients on anticoagulation than in patients off anticoagulation at 1 year in the unprovoked group (on: 3.7% vs. off: 12.2%, P<0.001), but not in the transient risk and cancer groups (respectively, 1.6% vs. 2.5%, P=0.30; 5.6% vs. 8.6%, P=0.44). CONCLUSIONS: The duration of anticoagulation therapy varied widely in discordance with current guideline recommendations. Optimal duration of anticoagulation therapy should be defined according to the risk of recurrent VTE and bleeding as well as death.
  • PCI後のプロタミンによる抗凝固能の適切な中和をめざして 止血時ACT減少に関わる影響因子の研究
    玉田 博之; 杉谷 勇季; 石川 千紗都; 大江 健太郎; 東儀 圭則; 城谷 学
    日本心血管インターベンション治療学会抄録集 (一社)日本心血管インターベンション治療学会 26回 MO162 - MO162 2017/07
  • 直接的血管形成による治療後の急性心筋梗塞において、入院時glucose値は梗塞サイズを反映し、結果として院内死亡率も示す可能性がある(Admission Glucose Levels may Reflect Infarct Size and Thereby in-hospital Mortality in Acute Myocardial Infarction Treated by Primary Angioplasty)
    杉谷 勇季; 玉田 博之; 太居 洋平; 石川 千紗都; 大江 健太郎; 三岡 仁和; 東儀 圭則; 横田 良司; 城谷 学
    日本循環器学会学術集会抄録集 (一社)日本循環器学会 81回 PJ - 201 2017/03
  • Uemori Noritsugu; Yokota Ryoji; Ohi Yohei; Ishikawa Chisato; Tamada Hiroyuki; Sugitani Yuuki; Ohe Kentarou; Mitsuoka Hirokazu; Togi Kiyonori; Shirotani Manabu
    Acta Medica Kinki University 近畿大学医学会 40 (2) 47 - 51 0386-6092 2015/12 
    症例は47歳女性で、6歳時にファロー四徴症に対する心内修復術の施行歴があった。今回、心悸亢進と目眩を主訴に来院した。心電図で心房周期240msの心房頻拍を認めた。心拍数は125bpmで、房室ブロックを認めた。多電極カテーテルを右房、右室、冠状静脈洞に挿入し、サンプリングレート1000/秒で心内心電図を記録した。磁気立体マッピング法の使用により高密度のactivation mapが30分間で作製できた。このactivation mapにより上大静脈と下大静脈をそれぞれ旋回するdual-loopの8の字型リエントリー回路が同定された。右房側壁の低電位領域にcritical isthmusを同定し、カテーテルアブレーションによりisthmusの先端から下大静脈に向かって焼却した。リエントリー性頻拍は根治し、右横隔神経の損傷は見られなかった。
  • 橫田良司; 玉田博之; 杉谷勇季; 太居洋平; 石川千紗都; 上森宜嗣; 三岡仁和; 東儀圭則; 胡内一郎; 城谷 学
    心電図 (一社)日本不整脈心電学会 34 (4) 382 - 389 0285-1660 2015/04 [Refereed]
     
    症例は53歳、男性。家族歴に特記すべきことなし。50歳の健診で心室期外収縮(PVC)を指摘されたが、症状なく放置。その後3年間に失神を5回、就寝中の尿失禁を2回経験した。失神はすべて座位で生じた。この間、トレッドミル試験で右室流出路起源と考えられるPVCが誘発され、他院でヘッドアップチルト試験により血管弛緩型の反射性失神と診断された。5回目の失神は自然回復せず、救急隊により自動体外式除細動器で心室細動が確認され、除細動された。搬送中の心電図モニターではPVCをきっかけに多形性心室頻拍が繰り返されていた。12誘導心電図はBrugada型ST上昇や早期再分極、J波を示さなかった。ICD植込み9ヵ月後、早朝就寝中に適切作動し除細動された。特発性心室細動で反射性失神と運動により誘発される右室流出路起源PVCを合併し、示唆に富む症例と考えられたため、ここに報告する。(著者抄録)
  • Incidence and Clinical Predictors of Stent Restenosis and Early Stent Occlusion in Patients with Acute Myocardial Infarction Treated by Bare Metal Stents: Importance of Infarct Location and Serum Creatinine Level
    Noritsugu Uemori; Yuki Sugitani; Hiroyuki Tamada; Yohei Ohi; Chisato Ishikawa; Narimasa Miho; Hirokazu Mitsuoka; Kiyonori Togi; Ichiro Kouchi; Ryoji Yokota; Manabu Shirotani
    Angiology 2 (4) 136  2014/11 [Refereed]
  • Short communication： Current Problems in the Treatment of Acute Myocardial Infarction: For Better Reperfusion and Long-Term Benefits
    Shirotani M; Togi K; Ohi Y
    Emergency Medicine 4 (6) 220  2014/09 [Refereed][Invited]
  • Editorial: What do we need to seek in the next step in clinical cardiology for better treatment of patients with cardiovascular diseases?
    Manabu Shirotani; Kiyonori Togi; Noritsugu Uemori
    Austin J Clin Cardiol 1 (1) 5  2014/01 [Refereed]
  • Hironobu Matsumae; Yoshinori Yoshida; Koh Ono; Kiyonori Togi; Katsumi Inoue; Yutaka Furukawa; Yasuhiro Nakashima; Yoji Kojima; Masakiyo Nobuyoshi; Toru Kita; Makoto Tanaka
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LIPPINCOTT WILLIAMS & WILKINS 28 (6) 1077 - 1083 1079-5642 2008/06 [Refereed]
     
    Objective-CCN1 (Cyr61) is an extracellular matrix-associated protein involved in cell proliferation and survival. CCN1 is bound to vascular smooth muscle cells (VSMCs) via integrins and is expressed in VSMCs in atherosclerotic lesions, suggesting involvement in the regulation of vascular smooth muscle cell (VSMC) proliferation and atherosclerosis. We hypothesized that knockdown of CCN1 may inhibit VSMC proliferation and suppress neointimal hyperplasia. Methods and Results-We examined the effect of the knockdown of CCN1 using rat cultured VSMCs and a rat balloon injury model. CCN1 stimulated adhesion and migration of VSMCs in a dose-dependent manner, and this was blocked by an antibody for integrin alpha(6)beta(1). Moreover, knockdown of endogenous CCN1 by lentiviral delivery of siRNA significantly inhibited proliferation of VSMCs and the uptake of 5-bromo-2'-deoxyuridine (BrdU). Replenishment with recombinant CCN1 reversed the effect of siRNA knockdown. Interestingly, knockdown of CCN1 significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at days 14 and 28 after injury. Gene transfer of CCN1 to smooth muscle reversed the effect of CCN1 knockdown on neointimal formation. These results suggest that endogenous CCN1 regulates proliferation of VSMCs and neointimal hyperplasia. Conclusion-Inhibition of CCN1 may provide a promising strategy for the prevention of restenosis after vascular interventions.
  • Yoshinori Yoshida; Kiyonori Togi; Hironobu Matsumae; Yasuhiro Nakashima; Yoji Kojima; Hiromi Yamamoto; Koh Ono; Tomoyuki Nakamura; Toru Kita; Makoto Tanaka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 355 (3) 611 - 618 0006-291X 2007/04 [Refereed]
     
    CCN1 (Cyr61) is a secreted matricellular protein, mediating angiogenesis and cell Survival through interaction with integrins. Although CCN1 expression is induced in the heart during ischemia and pressure overload, its function in cardiac myocytes remains to be elucidated. We hypothesized that CCN1 may not only induce angiogenesis but may also have a direct effect on cardiac myocytes during ischemia. In this study, we investigated the effect of CCN1 on survival of cardiac myocytes under oxidative stress and examined a signal transduction pathway downstream of CCN1. A solid-phase binding assay demonstrated that CCN1 was bound to cardiac myocytes in a dose-dependent, saturable manner. Inactivation of beta 1 integrin in cardiac myocytes inhibited binding with CCN1, indicating that CCN1 was bound to cardiac myocytes via beta 1 integrin. Knockdown of endogenous CCN1 decreased the number of surviving cells under oxidative stress, while pretreatment of cardiac myocytes with recombinant CCN1 significantly increased the number of surviving cells. Moreover, TUNEL staining showed that CCN1 significantly decreased apoptotic cells. Furthermore, treatment of cardiac myocytes with CCN1 induced phosphorylation of Akt and extracellular signal-regulated kinase (FRK). Inactivation of beta 1 integrin inhibited CCN1-induced phosphorylation of these kinases and abolished the protective effect of CCN1. Moreover, pretreatment of cells with wortmannin completely blocked the protective effect of CCN1 oil cardiac myocytes under oxidative stress, indicating that the protective effect of CCN1 was mainly mediated by activation of Akt. The antiapoptotic, effect of CCN1 oil cardiac myocytes together with its proangiogenic property could be beneficial in the treatment of ischemic heart disease. (c) 2007 Elsevier Inc. All rights reserved.
  • T Kawamoto; K Togi; R Yamauchi; Y Yoshida; Y Nakashima; T Kita; M Tanaka
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE PROFESSOR D A SPANDIDOS 18 (1) 193 - 196 1107-3756 2006/07 [Refereed]
     
    Homer proteins are a family of scaffolding proteins which may play an important role in calcium signaling by facilitating the assembly of signaling complexes in neuronal cells. Among the three splice variants of Homer 1, Homer 1a is rapidly up-regulated by neural stimulation and may regulate the disassembly of signaling complexes mediated by Homer proteins. In spite of its potential importance in calcium signaling, the regulation of Homer 1a expression in cardiac myocytes has never been investigated. In this study, we examined the regulation of Homer 1a expression in cardiac myocytes. Homer 1a was significantly up-regulated by several hypertrophic agonists, including endothelin-1 (ET-1), phenylephrine, isoprotenerol and angiotensin-II, and ET-1 most strikingly induced Homer 1a expression. The induction of Homer 1a expression by ET-1 peaked at 2 h and inhibitors for mitogen-activated/extracellular signal regulated kinase (MEK) significantly suppressed the induction of Homer M. This study first clarified the regulation of Homer 1a expression in cardiac myocytes and demonstrated that ET-1 induced Homer 1a expression through the mitogen-activated protein kinase pathway.
  • K Togi; Y Yoshida; H Matsumae; Y Nakashima; T Kita; M Tanaka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 343 (1) 144 - 151 0006-291X 2006/04 [Refereed]
     
    Interventricular septum (IVS) formation is one of the key events in the development of a four-chambered heart. We previously showed that the basic helix-loop-helix transcription factor Hand1 plays an important role in the formation of the I VS. Here, we found that the other Hand gene, Hand2, regulated expansion, trabeculation, and IVS formation in the embryonic heart. In transgenic embryos expressing Hand2 in the whole ventricles, the boundary region between the left and right ventricles expanded outwards, resulting in complete absence of the IVS. Moreover, trabecular formation was observed even in a region where the IVS was expected to forte. In some transgenic embryos with heterogeneous expression of the transgene, a muscular septum did not form in a region where Hand2 was expressed, but an incomplete septum was identifiable in a region where Hand2 was not expressed, suggesting that septum formation was strictly regulated by the expression domain of Hand2. Furthermore. expression of trabecular markers including ANF, BHP, and connexin40 was significantly up-regulated in the ventricles of Hand2 transgenic embryos as swell as in H9c2 cells over-expressing Hand2. These results suggested that the absence of Hand2 expression in the interventricular boundary region inhibits expansion and trabeculation in this area, contributing to the proper formation of the IVS. (c) 2006 Elsevier Inc. All rights reserved.
  • Zhuge, X; H Kataoka; M Tanaka; T Murayama; T Kawamoto; H Sano; K Togi; R Yamauchi; Y Ueda; Y Xu; SI Nishikawa; T Kita; M Yokode
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE PROFESSOR D A SPANDIDOS 15 (6) 945 - 948 1107-3756 2005/06 [Refereed]
     
    The Snai-related proteins are zinc-finger transcription factors that play important roles in cell-fate determination. We previously cloned a novel Snai-related gene known as snail-related transcription factor of muscle cells (Smuc) or, more recently, as snail homologue 3 (Snai3). In the present study, we investigated the functional roles of Smuc using in situ hybridization analysis at various stages of mouse development. Smuc was not detected until 12.5 days post-coitus (dpc). Its expression was observed in the skeletal muscles and thymus at 13.5 and 15.5 dpc, respectively, and these remained the major sites of Smuc expression until postnatal day 2. No Smuc expression was observed in the heart, large vessels, lungs, liver, kidney or brain. These results indicate that Smuc might be involved in the morphogenesis of the skeletal muscles and thymus at a relatively late stage of mouse development.
  • K Togi; T Kawamoto; R Yamauchi; Y Yoshida; T Kita; M Tanaka
    MOLECULAR AND CELLULAR BIOLOGY AMER SOC MICROBIOLOGY 24 (11) 4627 - 4635 0270-7306 2004/06 [Refereed]
     
    ,Molecular mechanisms for the dorso-ventral patterning and interventricular septum formation in the embryonic heart are unknown. To investigate a role of Hand1/eHAND in cardiac chamber formation, we generated Hand1/eHAND knock-in mice where Hand1/eHAND cDNA was placed under the control of the MLC2V promoter. In Hand1/eHAND knock-in mice, the outer curvature of the right and left ventricles expanded more markedly. Moreover, there was no interventricular groove or septum formation, although molecularly, Hand1/eHAND knock-in hearts had two ventricles. However, the morphology of the inner curvature of the ventricles, the atrioventricular canal, and the outflow tract was not affected by Hand1/eHAND expression. Furthermore, expression of Hand1/eHAND in the whole ventricles altered the expression patterns of Chisel, ANF,, and Hand2/dHAND but did not affect Tbx5 expression. In contrast, the interventricular septum formed normally in transgenic embryos overexpressing Hand1/eHAND in the right ventricle but not in the boundary region. These results suggested that Hand1/eHAND is involved in expansion of the ventricular walls and that absence of Hand1/eHAND expression in the boundary region between the right and left ventricles may be critical in the proper formation of the interventricular groove and septum. Furthermore, Hand1/eHAND is not a master regulatory gene that specifies the left ventricle myocyte lineage but may control the dorso-ventral patterning in concert with additional genes.
  • R Yamauchi; M Tanaka; N Kume; M Minami; T Kawamoto; K Togi; T Shimaoka; S Takahashi; J Yamaguchi; T Nishina; M Kitaichi; M Komeda; T Manabe; S Yonehara; T Kita
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LIPPINCOTT WILLIAMS & WILKINS 24 (2) 282 - 287 1079-5642 2004/02 [Refereed]
     
    Objective-SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8(+) T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease. Methods and Results-Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8(+) T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8(+) T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-gamma (IFN-gamma) production by CD8(+) T cells. Conclusions-SR-PSOX/CXCL16 may be involved in CD8(+) T cell recruitment through VLA-4 activation and stimulation of IFN-gamma production by CD8(+) T cells during inflammatory valvular heart disease.
  • SAKATA K.
    Hypertension 33 (6) 1447 - 1452 1999/06 [Refereed]

Conference Activities & Talks

  • 心臓マッサージ中にICDが作動した１症例  [Not invited]
    横田 良司; 石川 千紗都; 上森 宜嗣; 太居 洋平; 三保 成正; 東儀 圭則; 胡内 一郎; 城谷 学
    第13回京大関西心不全と不整脈カンファレンス  2013/02  大阪市  第13回京大関西心不全と不整脈カンファレンス
  • 下大静脈フィルター内血栓症の治療に難渋した肺塞栓症の一例  [Not invited]
    三保 成正; 城谷 学; 横田 良司; 胡内 一郎; 東儀 圭則; 上森 宜嗣; 石川 千紗都; 太居 洋平
    第20回日本心血管インターベンション治療学会近畿地方会  2013/02  大阪  第20回日本心血管インターベンション治療学会近畿地方会
  • 亜急性期にICD active leadが穿孔した心サルコイドーシスの一例  [Not invited]
    横田 良司; 石川 千紗都; 上森 宜嗣; 太居 洋平; 三保 成正; 東儀 圭則; 胡内 一郎; 城谷 学
    第12回京大関西心不全と不整脈カンファレンス  2012/08  大阪市  第12回京大関西心不全と不整脈カンファレンス

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