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Abstract 12144: Impact of Left Ventricular Diastolic Dysfunction on Long-Term Outcomes Following Coronary Artery Bypass Grafting: 5-Year Outcomes of the CREDO-Kyoto CABG Registry Cohort-2
- Akira Marui,
- Noboru Nishiwaki,
- Tatsuhiko Komiya,
- Michiya Hanyu,
- Shiro Tanaka,
- Takeshi Kimura,
- Ryuzo Sakata
Circulation Volume 130, Issue suppl_225 November 2014

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Background: Left ventricular (LV) systolic dysfunction (heart failure [HF] with low ejection fraction [EF]) is regarded as an independent risk factor for poor outcomes after coronary artery bypass grafting (CABG). However, the impact of LV diastolic dysfunction (HF with normal LVEF) still has been unclear.Methods and Results: We identified 1877 patients who received isolated CABG among 15,939 patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto Registry Cohort-2. Among them, 1489 patients had normal LV function (LVEF>50% without a history of HF; Normal group), 236 had LV systolic dysfunction (LVEF≤50% with HF; LVSD group), and 152 had LV diastolic dysfunction (LVEF>50% with HF; LVDD group). Preoperative LVEF in the LVSD group (36±9%) was markedly lower than the Normal (62±12%) and the LVDD groups (61±7%) (p<0.0001). [Table/Figure] In-hospital mortality in the LVDD group was equivalent to the Normal group (1.3% vs. 1.0%, p=0.72). However, cumulative all-cause mortality at 5-year in the LVDD group (32.1%) was higher than the Normal (13.7%) or the LVSD group (27.1%) (p<0.0001). Multivariate analysis showed that the risk of all-cause death in the LVDD group was higher than the Normal group (hazard ratio [95% confidence interval]: 1.43 [1.03-1.98], p=0.03). In addition, the risk of all-cause death in the LVDD group was equivalent to the LVSD group (0.89 [0.62-1.29], p=0.54). Furthermore, the risks of cardiac death and sudden death in the LVDD group were markedly higher than the Normal group (2.07 [1.27-3.36], p<0.01 and 3.60 [1.55-8.36], p<0.01), and the risks of those endpoints were not different between the LVSD and the LVDD groups.Conclusions: In spite of low in-hospital mortality after CABG in patients with LV diastolic dysfunction, they were associated with higher risks of long-term death and cardiovascular events. Patients with LV diastolic dysfunction, as well as LV systolic dysfunction, should be carefully operated and followed-up.
Abstract 11800: Optimal Coronary Revascularization in Patients With Unstable Angina or Non-ST-Elevation Myocardial Infarction: 5-Year Outcomes of the CREDO-Kyoto PCI/CABG Registry Cohort-2
- Akira Marui,
- Takeshi Kimura,
- Noboru Nishiwaki,
- Kazuaki Mitsudo,
- Tatsuhiko Komiya,
- Michiya Hanyu,
- Hiroki Shiomi,
- Shiro Tanaka,
- Ryuzo Sakata
Circulation Volume 130, Issue suppl_225 November 2014

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Background: SYNTAX trial revealed the long-term benefit of coronary artery bypass grafting (CABG) relative to percutaneous coronary intervention (PCI) using drug-eluting stent (DES) in patients with stable angina with complex coronary disease. However, long-term benefit of CABG relative to PCI in patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) has not been well elucidated.Methods and Results: We identified 673 patients with 3-vessel and/or left main disease with UA or NSTEMI among 15,939 patients undergoing first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2 (PCI: n=425, CABG: n=238). Age was not different between the 2 groups (p=0.58). Rate of Killip class III or IV (pulmonary edema or cardiogenic shock) was not different between the 2 groups (14% vs. 11%, p=0.19). Number of treated lesion was higher in the CABG group (2.0±1.0 vs. 3.0±1.0, p<0.001). Pre-procedural SYNTAX score was significantly higher in the CABG group (26.8±10.8 vs. 32.2±10.5, p<0.001). Unadjusted 30-day mortality was 6.0% for PCI and 2.9% for CABG.[Table] Five-year outcomes revealed that all-cause mortality after PCI was significantly higher than after CABG (hazard ratio [95% confidence interval]; 1.59 [1.15-2.21], p=0.005). The risk of composite of death, stroke, or myocardial infarction (MACCE) after PCI were also higher than after CABG (1.63 [1.23-2.16], p<0.001). In patients with 3-vessel disease without left main disease (n=465), the risks of death and MACCE after PCI were significantly higher than after CABG (1.59 [1.04-2.43], p=0.03 and 1.60 [1.10-2.34], p=0.01). Similarly the risks of death and MACCE after PCI were also higher than after CABG in patients with left main disease (n=208)Conclusions: In patients with UA or NSTEMI, 5-year outcomes revealed that CABG relative to PCI reduced the risk of death, MACCE, and any revascularization in the DES era both in patients with 3-vessel and left main disease.
Abstract 15745: Surgical Ineligibility and Long-term Clinical Outcome in Patients With Severe Coronary Artery Disease: The CREDO-Kyoto Registry Cohort-2
- Yukiko Matsumura-Nakano,
- Hiroki Shiomi,
- Takeshi Morimoto,
- Yutaka Furukawa,
- Yoshihisa Nakagawa,
- Kazushige Kadota,
- Kenji Ando,
- Kyohei Yamaji,
- Satoshi Shizuta,
- Ryuzo Sakata,
- Michiya Hanyu,
- Mitsuomi Shimamoto,
- Noboru Nishiwaki,
- Tatsuhiko Komiya and
- Takeshi Kimura
Circulation Volume 136, Issue suppl_114 November 2017

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Introduction: In patients with severe coronary artery disease (triple-vessel disease [3VD] and left main coronary artery disease [ULMCAD]) who require coronary revascularization in the real world clinical practice, the prevalence of surgical ineligibility and its clinical impact on long-term outcome remain unclear.Methods and Results: Among 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2, we identified 3,982 patients with 3VD or ULMCAD (percutaneous coronary intervention [PCI]: N=2188, coronary artery bypass grafting [CABG]: N=1794). The primary outcome measure was a composite of all-cause death, myocardial infarction, and stroke. Median follow-up duration was 1,863 days (interquartile range 1,534-2,166). Surgical ineligibility as documented in the hospital chart, was present in 142 out of 2188 patients receiving PCI (6.5%), which was mainly related to comorbidities and advanced age. The cumulative 5-year incidence of the primary outcome measure in PCI-patients with surgical ineligibility was much higher than that in PCI-patients without surgical ineligibility and in CABG-patients (52.5%, 27.6%, and 24.0%, respectively, log-rank P<0.001). After adjusting for confounders, the excess adjusted risks of PCI-patients with and without surgical ineligibility, respectively, relative to CABG-patients were significant (HR 1.98, 95%CI 1.52-2.59, P<0.001, and HR 1.38, 95%CI 1.52-2.59, P<0.001).Conclusions: In this retrospective analysis of patients with severe coronary artery disease (3VD/ULMCAD), patients who received PCI due to surgical ineligibility had a worse long-term outcome as compared with those without surgical ineligibility or CABG-patients. In the future observational comparison between PCI and CABG, prospective exclusion of patients with surgical ineligibility might be important to eliminate the influence of selection bias.
Very Long–Term (10 to 14 Year) Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Multivessel Coronary Artery Disease in the Bare-Metal Stent Era
- Hiroki Shiomi,
- Kyohei Yamaji,
- Takeshi Morimoto,
- Satoshi Shizuta,
- Kenji Nakatsuma,
- Hirooki Higami,
- Yutaka Furukawa,
- Yoshihisa Nakagawa,
- Kazushige Kadota,
- Kenji Ando,
- Ryuzo Sakata,
- Hitoshi Okabayashi,
- Michiya Hanyu,
- Mitsuomi Shimamoto,
- Noboru Nishiwaki,
- Tatsuhiko Komiya and
- Takeshi Kimura
Circulation: Cardiovascular Interventions Volume 9, Issue 81 August 2016

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Background—Many of the previous randomized trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary artery disease reported equivalent or better survival with CABG as compared with PCI at 5-year follow-up. However, 5-year follow-up might be too short to evaluate the true differences in long-term clinical outcomes between PCI and CABG.Methods and Results—Among 8934 patients enrolled in the extended 10- to 14-year follow-up study of the CREDO-Kyoto registry cohort-1 (Coronary Revascularization Demonstrating Outcome study in Kyoto) conducted in the bare-metal stent era, 5152 (PCI: n=3490 and CABG: n=1662) patients had multivessel coronary artery disease without left main disease. Median follow-up duration was 11.2 (interquartile range: 10.2–12.2) years. The cumulative 10-year incidence of all-cause death was not significantly different between PCI and CABG (32.2% versus 31.7%; log-rank P=0.93). After adjusting for confounders, however, the mortality risk of PCI was significantly higher than that of CABG (hazard ratio, 1.19 [95% confidence interval, 1.02–1.39]; P=0.03). Within 5 years after the index procedure, the risk for all-cause death was significantly higher after PCI than after CABG (hazard ratio, 1.41; 95% CI, 1.12–1.79; P=0.004). By a landmark analysis at 5 years, however, the cumulative 10-year incidence of and adjusted risk for all-cause death beyond 5 years were not significantly different between PCI and CABG (19.3% versus 20.0%; log-rank P=0.22 and hazard ratio, 1.02, 95% confidence interval, 0.83–1.26; P=0.82).Conclusions—CABG as compared with PCI was associated with better 10-year survival in patients with multivessel coronary artery disease. However, the benefit of CABG compared with PCI on late mortality beyond 5 years was not observed in this study.
Abstract 2979: Long-Term Clinical Outcome of Percutaneous Coronary Intervention With Bare Metal Stent for Unprotected Left Main Coronary Artery Disease Compared With Bypass Graft Surgery : From the CREDO-Kyoto
- Satoshi Shizuta,
- Takahiro Doi,
- Ryoji Taniguchi,
- Natsuhiko Ehara,
- Kei Nishiyama,
- Yutaka Furukawa,
- Ryozo Tatami,
- Teruaki Ushijima,
- Ryuichi Hattori,
- Noboru Nishiwaki,
- Masaru Tanaka,
- Kazuaki Minami,
- Yuki Sato,
- Saori Tezuka,
- Takeshi Morimoto,
- Satoshi Teramukai,
- Masanori Fukushima,
- Toru Kita,
- Takeshi Kimura
Circulation Volume 116, Issue suppl_1616 October 2007

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Background: The long-term safety and efficacy of percutaneous coronary intervention (PCI) for unprotected left main coronary artery (LMCA) disease compared with coronary artery bypass grafting (CABG) in the real clinical practice has not been well clarified.Methods: CREDO-Kyoto is a multi-center registry of Japanese patients (pts) undergoing first PCI or CABG between Jan. 2000 and Dec. 2002. Data of 9,877 consecutive pts from 30 institutions were available. Excluding those ≥ 80 years, 763 pts with LMCA disease were identified (PCI:82, CABG:681).Results: The baseline characteristics were as follows; Age≥ 75: 33 vs 21* (%); Male: 82 vs 74 (%); Previous MI: 18 vs 25 (%); CHF: 12 vs 24* (%); Hypertension: 90 vs 81* (%); Diabetes: 37 vs 45 (%); Creatinine > 1.2 (mg/dl): 17 vs 15 (%); Hyperlipidemia: 50 vs 56 (%); Smoker: 38 vs 38 (%); EF≤ 50%: 17 vs 24 (%); Isolated LMCA disease:22 vs 10* (%), (PCI vs CABG, *p<0.05). No drug-eluting but bare metal stent was used in PCI group. Twenty (24%) underwent atherectomy of LMCA before stenting. Off pump surgery was performed in 389 pts (57%), and internal thoracic artery was used in 632 pts (93%) of CABG group. None in PCI group but 25 (3.7%) in CABG group died during the hospitalization. During the follow-up period of 3.5±1.5 years, there were 90 deaths, including 62 cardiovascular (CV) deaths. The 4-year overall and CV survival was 83.6% and 89.7% in PCI group, corresponding to 88.9% and 92.6% in CABG group (p=NS). None in PCI group and 9 (1.3%) in CABG group died suddenly. The 4-year event free survival from CV death, MI, or cerebrovascular accident (MACE) was 82.0% and 84.2%, respectively (p=NS). The cumulative risk of any revascularization at 4-year was 50.8% and 14.9%, respectively (p<0.0001). In the multivariate analyses, age and renal dysfunction were the only independent predictors of long-term overall and CV mortality. Mode of revascularization neither affected long-term mortality nor MACE rate.Conclusions: PCI with bare metal stent is an alternative to CABG as an initial strategy for pts with unprotected LMCA disease in terms of similar long-term overall and MACE rate, though associated with a greater need for repeat revascularization.
Effects of Age and Sex on Clinical Outcomes After Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients With Triple-Vessel Coronary Artery Disease
- Kyohei Yamaji,
- Hiroki Shiomi,
- Takeshi Morimoto,
- Kenji Nakatsuma,
- Toshiaki Toyota,
- Koh Ono,
- Yutaka Furukawa,
- Yoshihisa Nakagawa,
- Kazushige Kadota,
- Kenji Ando,
- Shinichi Shirai,
- Tomoya Onodera,
- Hirotoshi Watanabe,
- Masahiro Natsuaki,
- Ryuzo Sakata,
- Michiya Hanyu,
- Noboru Nishiwaki,
- Tatsuhiko Komiya and
- Takeshi Kimura
Circulation Volume 133, Issue 1910 May 2016

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Background—Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice.Methods and Results—Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ≤65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10–1.79; P=0.006), whereas the risks were neutral in patients ≤65 years of age (HR, 1.05; 95% CI, 0.73–1.53; P=0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78–1.36; P=0.85; interaction P=0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03–1.50; P=0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98–1.84; P=0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P=0.40).Conclusions—There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG.
Incidence and Outcome of Surgical Procedures After Coronary Artery Bypass Grafting Compared With Those After Percutaneous Coronary Intervention: A Report From the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2
- Akihiro Tokushige,
- Hiroki Shiomi,
- Takeshi Morimoto,
- Koh Ono,
- Yutaka Furukawa,
- Yoshihisa Nakagawa,
- Kazushige Kadota,
- Kenji Ando,
- Satoshi Shizuta,
- Tomohisa Tada,
- Junichi Tazaki,
- Yoshihiro Kato,
- Mamoru Hayano,
- Mitsuru Abe,
- Shuichi Hamasaki,
- Mitsuru Ohishi,
- Hitoshi Nakashima,
- Kazuaki Mitsudo,
- Masakiyo Nobuyoshi,
- Toru Kita,
- Yutaka Imoto,
- Ryuzo Sakata,
- Hitoshi Okabayashi,
- Michiya Hanyu,
- Mitsuomi Shimamoto,
- Noboru Nishiwaki,
- Tatsuhiko Komiya and
- Takeshi Kimura
and on behalf of the CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators

Circulation: Cardiovascular Interventions Volume 7, Issue 41 August 2014

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Background—Noncardiac surgery after percutaneous coronary intervention (PCI) has been reported to be carrying high risk for both ischemic and bleeding complications. However, there has been no report comparing the incidence and outcomes of surgical procedures after coronary artery bypass grafting (CABG) with those after PCI.Methods and Results—Among 14 383 patients undergoing first coronary revascularization (PCI, n=12 207; CABG, n=2176) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) PCI/CABG Registry Cohort-2, surgical procedures were performed more frequently after CABG (n=560) than after PCI (n=2398; cumulative 3-year incidence: 27% versus 22%; unadjusted P<0.0001), particularly <6 months of coronary revascularization. The risk for the primary ischemic outcome measure (death/myocardial infarction) at 30-day postsurgical procedures was not significantly different between the CABG and PCI groups (cumulative incidence: 3.1% versus 3.2%; unadjusted P=0.9; adjusted hazard ratio, 0.97; 95% confidence interval, 0.47–1.89; P=0.9). The risk for the primary bleeding outcome measure (moderate or severe bleeding by Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries classification) was lower in the CABG groups than in the PCI group (cumulative incidence: 1.3% versus 2.6%; unadjusted P=0.07; adjusted hazard ratio, 0.36; 95% confidence interval, 0.12–0.87; P=0.02). There were no interactions between the timing of surgery and the types of coronary revascularization (CABG/PCI) for both ischemic and bleeding outcomes.Conclusions—Surgical procedures were performed significantly more frequently after CABG than after PCI, particularly <6 months after coronary revascularization. Surgical procedures after CABG as compared with those after PCI were associated with similar risk for ischemic events and lower risk for bleeding events, regardless of the timing after coronary revascularization.
Endothelial E-Selectin Potentiates Neovascularization via Endothelial Progenitor Cell–Dependent and –Independent Mechanisms
- Yasunobu Nishiwaki,
- Masayuki Yoshida,
- Hideki Iwaguro,
- Haruchika Masuda,
- Noriko Nitta,
- Takayuki Asahara and
- Mitsuaki Isobe
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 27, Issue 31 March 2007

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Background— Although potential participation of bone marrow-derived circulating endothelial progenitor cells (EPCs) to neoangiogenesis has been proposed, the precise molecular mechanisms of EPC recruitment to vascular endothelium has not been fully elucidated.Methods and Results— Peripheral blood mononuclear cells were isolated from healthy volunteers and cultured for 7 days to obtain EPCs. Tumor necrosis factor-α–activated human umbilical vein endothelial cells (HUVECs) supported significantly more rolling and adhesion of EPCs compared with inactivated HUVEC monolayer. Pretreatment of activated HUVEC with an adhesion-blocking mAb to E-selectin significantly reduced EPCs adhesion to HUVECs. When HUVECs were transduced with a recombinant adenovirus of E-selectin (AdRSVE-sel) or that of β-galactosidase (AdRSVLacZ), E-selectin-transduced but not LacZ-transduced HUVECs exhibited significantly more EPC rolling as well as adhesion. Further, effect of AdRSVE-sel or AdRSVLacZ was examined in mouse hind limb ischemic model. AdRSVE-sel–transduced mice showed significantly less limb necrosis and higher laser Doppler ratio when compared with AdRSVLacZ-transduced mice. Interestingly, blood flow recovery of ischemic limb observed in AdRSVE-sel–transduced mice was more prominent when combined with EPC administration compared with that of AdRSVLacZ-transduced mice.Conclusions— Endothelial E-selectin plays a crucial role in EPC–endothelial interaction in vitro. The importance of E-selectin was also confirmed in vivo even in the absence of exogenous EPC. These data provide molecular background for novel cell-based therapy for ischemic atherosclerosis.Although potential participation of bone marrow-derived circulating endothelial progenitor cells (EPCs) to neoangiogenesis has been proposed, the precise molecular mechanisms of EPC recruitment to vascular endothelium has not been fully elucidated.
Human Lecithin:Cholesterol Acyltransferase Deficiency: In Vivo Kinetics of Low-Density Lipoprotein and Lipoprotein-X
- Masato Nishiwaki,
- Katsunori Ikewaki,
- Giovanni Bader,
- Hassan Nazih,
- Minna Hannuksela,
- Alan T. Remaley,
- Robert D. Shamburek and
- H. Bryan Brewer
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 26, Issue 61 June 2006

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Objectives— Lecithin:cholesterol acyltransferase deficiency (LCAT-def) is characterized by low levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) and the accumulation of lipoprotein-X (LpX). Despite the low HDL, atherosclerosis is uncommon in LCAT-def. The decreased LDL would be a possible explanation but the underlying mechanism is not clear. In addition, the mechanism(s) for LpX accumulation is not known. The aim of the present study is to elucidate the mechanism(s) responsible for the low LDL and determine the plasma kinetics of LpX in LCAT-def.Methods and Results— We conducted a radiotracer study in LCAT-def (n=2) and normal controls (n=10) and a stable isotope study in one patient and other controls (n=7). LCAT-def LDL was catabolized faster than control LDL in the control subjects as well as in LCAT-def patients. Control LDL was catabolized faster in LCAT-def patients than the controls. The production rate of LDL apolipoprotein B-100 was normal in LCAT-def. The increased LDL apoB-100 catabolism was confirmed by a stable isotope study. LpX was catabolized more slowly in LCAT-def.Conclusions— The decreased LDL in LCAT-def is attributable to an increased catabolism caused by a rapid catabolism of abnormal LDL and an upregulation of LDL receptor pathway. The decreased catabolism of LpX contributes to its accumulation in LCAT-def.To elucidate the mechanism(s) responsible for the low LDL level in LCAT deficiency (LCAT-def), kinetic studies using radiotracers and a stable isotope were conducted in LCAT-def. Both studies revealed an increased catabolism of LDL. In addition, the radiotracer study showed a decreased catabolism of LpX in LCAT-def.
Abstract 14559: Monthly and Seasonal Variation in Sudden Cardiac Arrest Utstein Registry Study in Japan
- Kunihiro Nishimura,
- Yoshinori Miyamoto,
- Fumiaki Nakamura,
- Makoto Watanabe,
- Yuji Nishiwaki and
- Tomonori Okamura
Circulation Volume 124, Issue suppl_2122 November 2011

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Background : Previous studies have demonstrated seasonal variation in the incidence of acute myocardial infarction (AMI) with an increase in cases during the winter months. However, some studies showed negative association. We, therefore, examined seasonal variation in sudden cardiac arrest using 4 years of data from national database of cardiac arrest , the All-Japan Utstein Registry of the FDMAMethod: From January 1, 2005, through December 31, 2008, we conducted a prospective, population-based, observational study involving consecutive patients across Japan who had an out-of-hospital cardiac arrest and in whom resuscitation was attempted by emergency responders. Incidence rate ratio of fatal cardiac arrest and 95% Confidence Interval was calculated by monthly period.Result : A total of 431,844 adults who had an out-of-hospital cardiac arrest were included in this study; The incidence rates was highest in January and lowest with June.( 9.75 and 5.53, respectively). The incidence rate ratio of sudden cardiac arrest is 1.76(95%CI , 1.74-1.75, p<0.0001) This increasing relationship showed linear trend (P<0.0001 for trend. Fig1). These associations were robust after adjusting for age and sex. The resuscitation rate and 1 month survival showed no significant difference.Conclusion: Large population based registry showed monthly and seasonal variation in cardiac arrest. The risk of cardiac arrest is highest in winter and lower in mild climate season.
Abstract 12827: Impact of Concomitant Deep Vein Thrombosis on Clinical Outcomes in Patients With Acute Pulmonary Embolism
- Shushi Nishiwaki,
- Yugo Yamashita,
- Yusuke Morita,
- Moriaki Inoko,
- Takeshi Morimoto,
- Hidewo Amano,
- toru takase,
- Seiichi Hiramori,
- Kitae Kim,
- Maki Oi,
- Takao Kato and
- Takeshi Kimura
Circulation Volume 140, Issue Suppl_119 November 2019

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Introduction: For patients with acute pulmonary embolism (PE), risk stratification is important for decision-making regarding PE therapy. An increased thrombus burden such as concomitant deep venous thrombosis (DVT) might have a poor prognosis. Impact of concomitant DVT on short-term adverse events in acute PE patients has not been fully evaluated.Methods: The COMMAND VTE Registry was a retrospective multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) among 29 centers in Japan between 2010 and 2014. After excluding 1312 patients with DVT only and 1029 patients who did not undergo lower extremities ultrasound examination, the current study population consisted of 664 PE patients who underwent lower extremities ultrasound examination at diagnosis. There were 430 (64.8%) proximal DVT patients, 163 (24.5%) distal DVT patients, and 71 (10.7%) no-DVT patients. Outcome measures were compared among the 3 groups.Results: The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than those in distal DVT and no-DVT patients (proximal DVT: 7.8%, distal DVT: 2.5%, no-DVT: 2.8%, P=0.03). By multivariate analysis, the risk for all-cause death in proximal DVT patients tended to be higher than that in no-DVT patients (adjusted hazard ratio [HR], 2.28; 95% confidence interval [CI], 0.54-9.7, P=0.26), whereas the risk for all-cause death between distal DVT and no-DVT patients was comparable (adjusted HR, 0.88; 95% CI, 0.16-4.84, P=0.88). There was no significant difference for PE-related death, recurrent VTE, and major ISTH bleeding.Conclusions: The presence of concomitant proximal DVT was associated with a higher risk for short-term mortality in patients with acute PE. The examination of residual lower extremities thrombus could offer the advantages of further risk stratification and decision-making for acute PE.
Abstract MP45: Monday Morning Surge of Sudden Out-of-hospital Cardiac Arrest -from 63,620 Cases of Japanese Adults Aged 20-65 -All Japan Utstein Registry Study
- Kunihiro Nishimura,
- Tmonori Okamura,
- Michikazu Nakai,
- Misa Takegami,
- Satosshi Yasuda,
- Yuji Nishiwaki and
- Yoshihiro Miyamoto
Circulation Volume 127, Issue suppl_1226 March 2013

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Circadian and weekly variation in the incidence of out-of-hospital cardiac arrest (OHCA) was observed in previous studies. However, most of them are often small, regional, and not population based. We therefore examined circadian and weekly variation in sudden cardiac arrest using 4 years of data from national database of cardiac arrest registry, the All-Japan Utstein Registry of the FDMA (Fire and Disaster Management Agency), Japanese government.Method: From January 1, 2005, through December 31, 2008, we conducted a population-based, observational study involving consecutive patients across Japan who had an OHCA. Incidence rate ratio (IRR) of OHCA were calculated for every 3hours and day of week by Poisson regression analysis.Results: A total of 63,620 adults aged 20-65 who had an OHCA were included in this study; the pattern in the occurrence of OHCA is characterized by a marked bimodal peak at 6-8 o’clock and 15-17 o’clock (P for <0.001)(Figure1). Interestingly, the IRR of OHCA in the Monday morning was the highest 2.16 (95%CI: 1.99-2.35) compared with the midnight in Sunday (reference). These associations were robust after adjusting for age and sex. The incidence rate of OHCA in the morning is decreasing over the day of week and the lowest in Sunday (P<0.0001). The IRR for the Sunday morning was 1.56 (95% CI, 1.44-1.72).Conclusion: Large population based registry showed circadian and weekly variation variations in OHCA aged 20-65. The risk of cardiac arrest is highest in the morning and late afternoon. Monday morning was the highest risk and the mental stress of starting a new working week may be a cause.
Abstract P006: Association of Age, Temperature and Month-to-month Variation in Sudden Out-of-hospital Cardiac Arrest Due Stroke of 21,986 Cases -All Japan Utstein Registry Study
- Kunihiro Nishimura,
- Tomonori Okamura,
- Michikazu Nakai,
- Misa Takegami,
- Tanvir C Turin,
- Yuji Nishiwaki and
- Yoshihiro Miyamoto
Circulation Volume 127, Issue suppl_1226 March 2013

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Aims: To examine whether month-to-month trend of out-of-hospital cardiac arrest (OHCA) due to stroke existed and to investigate its relationship with age, sex and the mean lowest temperatures.Method and Result: From 2005 to 2008, we conducted a population-based, prospective observational study on OHCA using national database of cardiac arrest registry.A total of 21,986 adults, aged >=20 with OHCA due to stroke were included in this study; the trend is characterized by a marked peak in January (P <0.0001). The IRR in January was 1.90(95%CI: 1.78-2.03).These associations were robust after adjusting by age and sex and more marked indicated as aging. ( OR for age>=80=2.07(95%CI 1.85-2.32). The IRR for the lowest temperature adjusted by age, sex and month was 0.945 (p<0.001). When the lowest temperature decreases by one degree, OHCA risk increases 5.8%Conclusion: Large population based on registry showed monthly variations in OHCA due to stroke. The risk of cardiac arrest due to stroke was the highest in January and lower in mild climate season. The aging and the low temperatures were high-risk of cardiac arrest.
Abstract 16400: Development of Deep Neural Network Models for Identification of Pulmonary Vein Potentials From Body Surface Electrocardiograms of Patients With Atrial Fibrillation
- Munekazu Tanaka,
- Hirohiko Kohjitani,
- Tomoyuki Inoue,
- Akifumi Morinaga,
- Fumiya Yoneda,
- Shushi Nishiwaki,
- Satoshi Shizuta,
- Yasushi Okuno and
- Koh Ono
Circulation Volume 148, Issue Suppl_17 November 2023

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[Background] Pulmonary vein (PV) potential is essential as the origin of atrial fibrillation (AF). However, no established method exists to evaluate PV potentials on a body surface ECG (BS-ECG).[Objective] To develop a method to identify PV potentials from BS-ECGs using state-of-the-art deep neural network (DNN) technology.[Methods and results] A cohort of 799 consecutive paroxysmal AF patients, who underwent Pulmonary Vein Isolation (PVI), were enrolled, and pre- and post-PVI 12-lead ECGs (12ECGs) were collected, amounting to a dataset of 1598 ECGs. Four DNN models were constructed, each employing distinct architectures: 1D-ResNet, 1D-DenseNet, 1D-EfficientNet-b3, and 1D-ViT (Vision Transformer). These models were rigorously trained and evaluated for the identification of PV potentials. The 1D-EfficientNet-b3-based model exhibited optimal performance, achieving an accuracy of 89.4% in the training set and 89.1% in the test set. The Gradient-weighted Class Activation Mapping (Grad-CAM) effectively demonstrated that the segments 200-300ms before the P-wave is crucial for identifying PV potentials. Furthermore, DNN models were developed for each single-lead ECG. While there were variations in the accuracy of PV potential identification among single-lead models, the V6-lead model demonstrated superior performance with an accuracy of 83.2%.[Conclusions] The findings of this research strongly suggest that our DNN-based model can accurately differentiate PV potentials from BS-ECGs. Additionally, Grad-CAM visualizations indicate that pertinent features for the identification of PV potentials are predominantly clustered in the P-wave frontal region. This signifies a promising advancement in the non-invasive detection and analysis of PV potentials, paving the way for improved management of paroxysmal AF.
Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry
- Kenji Nakatsuma,
- Tomohiko Taniguchi,
- Takeshi Morimoto,
- Hiroki Shiomi,
- Kenji Ando,
- Norio Kanamori,
- Koichiro Murata,
- Takeshi Kitai,
- Yuichi Kawase,
- Chisato Izumi,
- Makoto Miyake,
- Hirokazu Mitsuoka,
- Masashi Kato,
- Yutaka Hirano,
- Shintaro Matsuda,
- Tsukasa Inada,
- Kazuya Nagao,
- Tomoyuki Murakami,
- Yasuyo Takeuchi,
- Keiichiro Yamane,
- Mamoru Toyofuku,
- Mitsuru Ishii,
- Eri Minamino‐Muta,
- Takao Kato,
- Moriaki Inoko,
- Tomoyuki Ikeda,
- Akihiro Komasa,
- Katsuhisa Ishii,
- Kozo Hotta,
- Nobuya Higashitani,
- Yoshihiro Kato,
- Yasutaka Inuzuka,
- Chiyo Maeda,
- Toshikazu Jinnai,
- Yuko Morikami,
- Naritatsu Saito,
- Kenji Minatoya,
- Takeshi Kimura
and the CURRENT AS Registry Investigators^†

Journal of the American Heart Association Volume 6, Issue 7

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BackgroundThere are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS).Methods and ResultsAmong 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax <4.5 m/s, N=550; group 2, 4.5 ≤ Vmax <5 m/s, N=279; and group 3, Vmax ≥5 m/s, N=246). Cumulative 5‐year incidence of AS‐related events (aortic valve–related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS‐related events remained significant (hazard ratio, 1.39; 95% CI, 1.07–1.81; P=0.02, and hazard ratio, 1.53; 95% CI, 1.17–2.00; P=0.002, respectively). The effect size of group 3 relative to group 1 for AS‐related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI, 1.01–2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16–2.40, P=0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS‐related events (interaction, P=0.88).ConclusionsIn conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS‐related events. However, the cumulative 5‐year incidence of the AS‐related events remained very high even in asymptomatic patients with less greater Vmax.
Prognostic Impact of Aortic Valve Area in Conservatively Managed Patients With Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction
- Norio Kanamori,
- Tomohiko Taniguchi,
- Takeshi Morimoto,
- Hirotoshi Watanabe,
- Hiroki Shiomi,
- Kenji Ando,
- Koichiro Murata,
- Takeshi Kitai,
- Yuichi Kawase,
- Chisato Izumi,
- Makoto Miyake,
- Hirokazu Mitsuoka,
- Masashi Kato,
- Yutaka Hirano,
- Shintaro Matsuda,
- Kazuya Nagao,
- Tsukasa Inada,
- Hiroshi Mabuchi,
- Yasuyo Takeuchi,
- Keiichiro Yamane,
- Mamoru Toyofuku,
- Mitsuru Ishii,
- Eri Minamino‐Muta,
- Takao Kato,
- Moriaki Inoko,
- Tomoyuki Ikeda,
- Akihiro Komasa,
- Katsuhisa Ishii,
- Kozo Hotta,
- Nobuya Higashitani,
- Yoshihiro Kato,
- Yasutaka Inuzuka,
- Chiyo Maeda,
- Toshikazu Jinnai,
- Yuko Morikami,
- Naritatsu Saito,
- Kenji Minatoya,
- Takeshi Aoyama,
- Takeshi Kimura
and the CURRENT AS Registry Investigators ^†

Journal of the American Heart Association Volume 8, Issue 35 February 2019

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BackgroundData are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database.Methods and ResultsAmong 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm², N=645; group 2: 0.8 cm² ≥AVA >0.6 cm², N=465; and group 3: AVA ≤0.6 cm², N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56–3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01–1.78, P=0.04, respectively).ConclusionsAVA ≤0.6 cm² would be a useful marker to identify those high‐risk patients with asymptomatic severe AS, who might benefit from early AVR.Clinical Trial RegistrationURL: www.umin.ac.jp. Unique identifier: UMIN000012140.See Editorial by Tribouilloy et al
Clinical Efficacy of Thrombus Aspiration on 5‐Year Clinical Outcomes in Patients With ST‐Segment Elevation Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention
- Hiroki Watanabe,
- Hiroki Shiomi,
- Kenji Nakatsuma,
- Takeshi Morimoto,
- Tomohiko Taniguchi,
- Yutaka Furukawa,
- Yoshihisa Nakagawa,
- Minoru Horie,
- Takeshi Kimura
and the CREDO‐Kyoto AMI investigators^†

Journal of the American Heart Association Volume 4, Issue 6

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BackgroundAdjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long‐term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long‐term clinical outcomes in patients with ST‐segment elevation myocardial infarction (STEMI) undergoing primary PCI.Methods and ResultsThe CREDO‐Kyoto AMI Registry is a large‐scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005–2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5‐year incidence of all‐cause death was significantly lower in the TA group than in the non‐TA group (18.5% versus 23.9%, log‐rank P<0.001). After adjusting for confounders, however, the risk for all‐cause death in the TA group was not significantly lower than that in the non‐TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target‐lesion revascularization were also not significantly different between the 2 groups.ConclusionsAdjunctive TA during primary PCI was not associated with better 5‐year mortality in STEMI patients.
Beneficial Effects of Alcohol Withdrawal on LDL Particle Size Distribution and Oxidative Susceptibility in Subjects With Alcohol-Induced Hypertriglyceridemia
- Makoto Ayaori,
- Toshitsugu Ishikawa,
- Hiroshi Yoshida,
- Michio Suzukawa,
- Masato Nishiwaki,
- Hideki Shige,
- Toshimitsu Ito,
- Kei Nakajima,
- Kenji Higashi,
- Atsushi Yonemura and
- Haruo Nakamura
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 17, Issue 111 November 1997

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Abstract LDL subclass pattern B, reported to have a higher prevalence in hypertriglyceridemics (HTGs), is considered to be associated with an increased risk for coronary artery disease, and the small dense LDL characteristic of this pattern is susceptible to oxidative modification. Alcohol is considered one of the most frequent causes of increases in plasma triglyceride (TG) levels. We investigated the effects of alcohol withdrawal on LDL subclass distribution and oxidizability in drinkers with different plasma TG levels. Thirty-seven male subjects with relatively heavy alcohol-consumption habits were divided into four groups; normotriglyceridemic (NTG)/withdrawal (n=11), NTG/control (n=8), hypertriglyceridemic (HTG)/withdrawal (n=10), and HTG/control (n=8). Both withdrawal groups abstained form alcohol for 4 weeks, while the control subjects maintained their usual intake of alcohol. Peak LDL particle diameter (PPD) was smaller in the combined HTG groups than in the combined NTG groups before abstinence, although PPD increased significantly (P<.01) from 25.5 to 26.1 nm in the HTG/withdrawal group. Before abstinence, lag times preceding LDL oxidation in the combined HTG groups were shorter than in the combined NTG groups; after withdrawal, lag time was prolonged significantly (P<.01) from 49.9 to 57.3 minutes in the HTG-withdrawal group. No significant changes in PPD and lag time were observed in the other three groups. Significant correlations (P<.05) were observed between the change (Δ) in lag time and ΔTG and between Δlag time and ΔPPD. We conclude that in alcohol-induced HTG subjects, alcohol withdrawal has beneficial effects on the LDL profile by shifting the particle size from smaller to larger and decreasing its susceptibility to oxidation.
Targeted Delivery of Bone Marrow Mononuclear Cells by Ultrasound Destruction of Microbubbles Induces Both Angiogenesis and Arteriogenesis Response
- Takanobu Imada,
- Tetsuya Tatsumi,
- Yasukiyo Mori,
- Takashi Nishiue,
- Masayuki Yoshida,
- Hiroya Masaki,
- Mitsuhiko Okigaki,
- Hiroyuki Kojima,
- Yoshihisa Nozawa,
- Yasunobu Nishiwaki,
- Noriko Nitta,
- Toshiji Iwasaka and
- Hiroaki Matsubara
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 25, Issue 101 October 2005

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Objective— Ultrasound (US)-mediated destruction of contrast microbubbles causes capillary rupturing that stimulates arteriogenesis, whereas intramuscular implantation (im) of bone marrow mononuclear cells (BM-MNCs) induces angiogenesis. We therefore studied whether US-targeted microbubble destruction combined with transplantation of BM-MNCs can enhance blood flow restoration by stimulating both angiogenesis and arteriogenesis.Methods and Results— US-mediated destruction of phospholipid-coated microbubbles was applied onto ischemic hindlimb muscle and subsequently BM-MNCs were transfused. A significant enhancement in blood flow recovery after Bubble+US+BM-MNC infusion (34% increase, P<0.05) was observed compared with Bubble+US (25%). The ratio of capillary/muscle fiber increased by Bubble+US+BM-MNC-i.v (260%, P<0.01) than that in the Bubble+US group (172%), into which BM-MNCs were incorporated (angiogenesis). Smooth muscle α-actin–positive arterioles were also increased, and angiography showed augmented collateral vessel formation (arteriogenesis). Platelet-derived proinflammatory factors activated by Bubble+US induces the expression of adhesion molecules (P-selectin and ICAM-1), leading to the attachment of transplanted BM-MNCs on the endothelium. Flow assay confirmed that the platelet-derived factors cause the adhesion of BM-MNCs onto endothelium under laminar flow.Conclusions— This study demonstrates that the targeted delivery of BM-MNCs by US destruction of microbubbles enhances regional angiogenesis and arteriogenesis response, in which the release of platelet-derived proinflammatory factors activated by Bubble+US play a key role in the attachment of transplanted BM-MNCs onto the endothelial layer.Ultrasound (US)-targeted microbubble destruction combined with transplantation of bone marrow mononuclear cells (BM-MNCs) enhances blood flow restoration by stimulating both angiogenesis and arteriogenesis. Release of proinflammatory factors from platelets activated by Bubble+US play a key role for adhesion of BM-MNCs on endothelium. This cell delivery system is efficient for therapeutic angiogenesis and arteriogenesis.
Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells
- Soichiro Fujiyama,
- Katsuya Amano,
- Kazutaka Uehira,
- Masayuki Yoshida,
- Yasunobu Nishiwaki,
- Yoshihisa Nozawa,
- Denan Jin,
- Shinji Takai,
- Mizuo Miyazaki,
- Kensuke Egashira,
- Takayuki Imada,
- Toshiji Iwasaka and
- Hiroaki Matsubara
Circulation Research Volume 93, Issue 1014 November 2003

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Peripheral blood (PB)-derived CD14⁺ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34⁻/CD14⁺ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34⁻/CD14⁺ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34⁺ cells. MCP-dependent adhesion was not observed in PB-derived CD34⁻/CD14⁺ monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and β₁-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating β₁-integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34⁺ cells and acquire the ability to adhere on injured endothelium in a MCP-1–dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1–mediated biological actions and vascular regeneration strategies by cell therapy.

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