Yoichi Kuwabara - Academia.edu (original) (raw)
Papers by Yoichi Kuwabara
Circulation, Apr 25, 2006
Hypertension Research, 2011
Hypertension Research, 2008
Antihypertensive therapy has been well established to reduce hypertension-related morbidity and m... more Antihypertensive therapy has been well established to reduce hypertension-related morbidity and mortality, but the optimal therapy for Japanese patients remains unknown. The Valsartan Amlodipine Randomized Trial (VART), a prospective randomized open-label trial, was designed to determine whether treatment with an angiotensin II type 1 receptor blocker (valsartan) or a calcium channel blocker (amlodipine) lowers cardiovascular disease events in essential hypertensives in Japan. Registration, randomization and data entry were performed over the Internet. The minimization method (to control for age, gender, blood pressure level and history) was used at random assignment to ensure that the background factors were equivalent between the groups at baseline. After the registration, patients were followed-up for cardiovascular events (primary endpoints), echocardiography, 123 I-metaiodobenzylguanidine (MIBG) imaging, laboratory tests and blood pressure for 3 years. Currently, 797 patients have been enrolled and assigned to two groups: a valsartan (n =399) and an amlodipine (n =398) group. At baseline, controlled factors (age, gender, blood pressure level, and left ventricular hypertrophy) and the proportions of patients with diabetes and hyperlipidemia were equally allocated. At 12 months, both drugs evenly and significantly lowered blood pressure to the target level (valsartan: 133/79 mmHg; amlodipine: 132/79 mmHg). In conclusion, by combining the data on cardiovascular events with the results of echocardiographic, radionuclide imaging, and blood/urine studies, the VART study will provide mechanistic insights into the clinical outcomes and treatment effects of the trial.
Journal of Human Hypertension, Aug 14, 2013
The paper has been retracted due to concerns raised by the publishing institution regarding probl... more The paper has been retracted due to concerns raised by the publishing institution regarding problems with management of conflicts of interest and with the reliability of the published data.
Circulation journal, 2004
hurg-Strauss syndrome (CSS) is characterized by asthma, eosinophilia, and systemic necrotizing va... more hurg-Strauss syndrome (CSS) is characterized by asthma, eosinophilia, and systemic necrotizing vasculitis, and cardiac involvement (ie, eosinophilic heart disease 1,2) is the major cause of morbidity and mortality. 1,3 However, there are no reports of an association between left ventricular dysfunction caused by eosinophilic heart disease and myocardial blood flow or myocardial fatty acid metabolism. We describe a patient with CSS and eosinophilic heart disease that progressed to dilated cardiomyopathy and which exhibited abnormal myocardial fatty acid metabolism on myocardial scintigraphy.
Hypertension Research, 2016
European Heart Journal, 2013
Mineralocorticoid receptor antagonists have been shown to be beneficial in treatment and mortalit... more Mineralocorticoid receptor antagonists have been shown to be beneficial in treatment and mortality reduction in heart failure with reduced ejection fraction in randomized trials. Data regarding their usefulness in HFPEF remains to be studied. We studied the effects of spironolacton (S) on diastolic stiffness and LV remodeling in diabetic pts with HFPEF. Methods: 137 pts 64±12 yrs (56% female) with HFPEF NYHA III with diabetes mellitus and without renal failure were randomized to two groups in order to receive S on top of their treatment (n=68) 25mg/day to further increase to 50mg/day after 8 weeks if no hyperkalemia (>5.5 mmol/l) has been developed or amilorid (A) 2.5 mg/day to increase to 5mg/day after 8 weeks in pts without hyperkalemia (n=69) for 6 months. Medications as ACEI/ARB, β-blockers, loop diuretics were evenly distributed in groups. NTproBNP levels, and diastolic wall stress (DWS) as (PWs-PWd) /PWs, LV mass index (LVMI), septal E/Em, LA volume index (LAVI) were measured by EchoCG by two independent observers unaware of the aim of the study in 1, 30, 90 and 180 days follow up. Results: In 30 days there were no significant changes in all parameters. In 90 day E/Em were significantly less in S compared with A (10.8±2.3 vs 12.1±3.1, p<0.05) without changes in other parameters. This difference remained unchanged throughout the study. In 180 days DWS, LVMI, LAVI and NTproBNP levels were significantly better in S group.
Circulation. Cardiovascular interventions, 2009
Injection of bone marrow mononuclear cells has been reported to promote neovascularization of isc... more Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of ...
Nihon rinsho. Japanese journal of clinical medicine, Jan 28, 2007
Movement Disorders, 2009
Deep brain stimulation (DBS) is successfully used for symptomatic treatment of various movement d... more Deep brain stimulation (DBS) is successfully used for symptomatic treatment of various movement disorders. However, the technique is not without risks for adverse events related to surgery, hardware, or stimulation itself. There is a continued need for standardized reporting of adverse events related to DBS surgery, especially with respect to serious infections. 1 These include the rare complication of intracerebral infections, which if not recognized, may cause serious and longterm morbidity. A 55-year-old man with tremor-predominant Parkinson's disease underwent unilateral DBS surgery. The electrode (3387, Medtronic, Minneapolis, MN) was placed in the right
Journal of the American College of Cardiology, 2004
Noninvasive Imaging sound system. Recent developed real time compound imaging, Sono CT, which sup... more Noninvasive Imaging sound system. Recent developed real time compound imaging, Sono CT, which suppresses the artifacts and reinforces real structures by scanning from different angles and averaging these independent frames, may detect IMT and calcified lesions noninvasively. Methods: We tried to measure IMT and evaluate calcified lesions of distal LAD using Sono CT after guiding usual TTDE (HDI 5000, Philips medical systems) in 33 patients (65.7± 9.3 years old) in whom IVUS catheter could be delivered to distal LAD area near Sono CT probe position on coronary intervention therapy for proximal LAD lesions. According to the usual TTDE probe position where the distal LAD flow was detected, we put the Sono CT probe, and tried to find coronary artery and to measure IMT and evaluate calcified lesions of the coronary artery. We confirmed Sono CT probe position was same as the location where we evaluated using IVUS in the catheter laboratory. Two independent echocardiographic experts analyzed whether IMT and calcified lesions could be detected or not. Results: In all the patients, anterior and posterior coronary artery wall could be detected, and in 21 (64%) among these 33 patients we could measure IMT using Sono CT. IMT of the anterior and posterior wall of the distal LAD were 0.5 ± 0.1mm and 0.4 ± 0.1mm, respectively. There were significant correlation between IMT that were measured by Sono CT and those by IVUS (y = 0.71x + 0.24, r = 0.52, P<0.05). Using Sono CT, the calcified lesions could be found in 3 patients in whom IVUS validated calcified lesion at the same portion of coronary arteries, however, usual TTDE could not detect all these three calcified lesions. Conclusion: IMT and calcified lesions of distal LAD can be assessed noninvasively and accurately using Sono CT.
Journal of the American College of Cardiology, 1997
Objectives. The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled s... more Objectives. The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Background. Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. Methods. One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. Results. Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p ؍ 0.001). Minimal lumen diameter was 1.49 ؎ 0.75 mm (mean ؎ SD) in the probucol group and 1.13 ؎ 0.65 mm in the control group (p ؍ 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p ؍ 0.009). The late loss was 0.37 ؎ 0.69 mm in the probucol group and 0.60 ؎ 0.62 mm in the control group (p ؍ 0.13). The loss/gain ratio was 0.32 ؎ 0.74 in the probucol group and 0.56 ؎ 0.81 in the control group (p ؍ 0.059). Net gain was greater in the probucol group than in the control group (0.77 ؎ 0.70 vs. 0.48 ؎ 0.59 mm, p ؍ 0.053). Conclusions. Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.
Journal of the American College of Cardiology, 2002
Background: Second hand smoke (SHS) contributes to endothelial dysfunction. We previously showed ... more Background: Second hand smoke (SHS) contributes to endothelial dysfunction. We previously showed that the angictensin II receptor blocker Iosartan improved endothelial dysfunction and myooadial ischemia. We sought to determine whether Iosartan prevents endothelial dysfunction and myocardial ischemia in rats exposed to SHS. Methods: 84 Sprague-Dawley rats were randomized to receive Iosartan (40 mg/kg/day) and/or SHS (smoking chamber) in a 2 by 2 design. The source of SHS was sidesream smoke of 4 cigarettes every 15 rain, 6 hours a day, 5 days a week. After 6 weeks, the rats were subjected to 17 min of LAD occlusion and 120 rain of reperfusion. In fresh aortic rings precontracted with phenylephrine, endothelium-dependent and-independent relaxation were assessed.Vascular endothelial growth factor (VEGF) in the ischemic myocardium was measured by Western blot analysis. Results: SHS impaired endothelial dependent relaxation to ecetylcholine and endothelial independent relaxation to nitroglycerin. Losartan reduced the impaired maximal vasorelaxation induced by A2.3187. Losarfan increased effective refractory period (ERP) and VF threshold. SHS increased infarct size and VEGF. Losadan decreased infarct size, but did not affect the increased infarct size caused by SHS. Conclusions: SHS impaired endothelial function and increased infarct size and VEGF. Losartan prevented endothelial dysfunction secondary to SHS, but did not affect the increased infarct size caused by SHS.
International Journal of Cardiology, 2007
Background: This study examined feasibility and safety of granulocyte colony-stimulating factor (... more Background: This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI). Methods: Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group (n = 18) or Control group (n = 22). G-CSF treatment was started within 24 h after PCI. 99m Tc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion. Results: LVEF at 6 months was significantly better than that at 4 days in G-CSF group (p = 0.013), but not changed in Control group (p = 0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups. Conclusions: G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.
Hypertension Research, 2001
Hypertension Research, 1992
Hypertension Research, 2008
Antihypertensive therapy has been well established to reduce hypertension-related morbidity and m... more Antihypertensive therapy has been well established to reduce hypertension-related morbidity and mortality, but the optimal therapy for Japanese patients remains unknown. The Valsartan Amlodipine Randomized Trial (VART), a prospective randomized open-label trial, was designed to determine whether treatment with an angiotensin II type 1 receptor blocker (valsartan) or a calcium channel blocker (amlodipine) lowers cardiovascular disease events in essential hypertensives in Japan. Registration, randomization and data entry were performed over the Internet. The minimization method (to control for age, gender, blood pressure level and history) was used at random assignment to ensure that the background factors were equivalent between the groups at baseline. After the registration, patients were followed-up for cardiovascular events (primary endpoints), echocardiography, 123 I-metaiodobenzylguanidine (MIBG) imaging, laboratory tests and blood pressure for 3 years. Currently, 797 patients have been enrolled and assigned to two groups: a valsartan (n =399) and an amlodipine (n =398) group. At baseline, controlled factors (age, gender, blood pressure level, and left ventricular hypertrophy) and the proportions of patients with diabetes and hyperlipidemia were equally allocated. At 12 months, both drugs evenly and significantly lowered blood pressure to the target level (valsartan: 133/79 mmHg; amlodipine: 132/79 mmHg). In conclusion, by combining the data on cardiovascular events with the results of echocardiographic, radionuclide imaging, and blood/urine studies, the VART study will provide mechanistic insights into the clinical outcomes and treatment effects of the trial.
Hypertension, 2000
Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, ... more Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, and abnormal glucose metabolism. However, no study has examined the relative pathological significance of left ventricular hypertrophy and abnormal glucose metabolism on endothelial dysfunction in hypertension. This study was conducted to evaluate whether abnormal glucose tolerance assessed by 75-g oral glucose tolerance test or left ventricular hypertrophy is more closely associated with endothelial dysfunction in never-treated hypertensive patients without elevated fasting blood glucose. We studied 107 unmedicated hypertensive patients (mean age, 54Ϯ10 years) whose fasting blood glucose was Ͻ7.0 mmol/L. Endothelial function was assessed by change in brachial artery diameter in response to reactive hyperemia, and left ventricular mass index was determined by ultrasonography. Simple linear regression analysis demonstrated that endothelial function significantly correlated with left ventricular mass index and 2-hour blood glucose in 75-g oral glucose tolerance test, but not with fasting blood glucose. Multiple linear regression analysis revealed that endothelial function significantly correlated with 2-hour blood glucose (ϭϪ2.68, PϽ0.05) after we controlled for other clinical variables. Patients were divided into 3 groups according to 2-hour blood glucose levels. Endothelial function was more impaired in patients with diabetes (nϭ12; 4.7Ϯ1.8%) and in those with impaired glucose tolerance (nϭ31; 6.3Ϯ2.9%) than in those with normal glucose tolerance (nϭ64; 8.4Ϯ4.5%) (PϽ0.05), but left ventricular mass index was similar in these 3 groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test, rather than left ventricular hypertrophy, may have direct pathophysiological relevance to endothelial dysfunction in borderline to moderate hypertensive patients.
Heart and Vessels, 2010
In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogre... more In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 mumol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% +/- 11% vs 38% +/- 15%, not significant) and 20 mumol/l adenosine diphosphate (48% +/- 13% vs 51% +/- 12%, not significant) between 50 mg clopidogrel and 200 mg ticlopidine. In Japanese patients, there is the possibility that a maintenance dose of 50 mg clopidogrel on platelet inhibition is comparable to 200 mg ticlopidine.
European Journal of Nuclear Medicine, 2000
To evaluate the relationship between the mental stress-induced decrease in left ventricular eject... more To evaluate the relationship between the mental stress-induced decrease in left ventricular ejection fraction (LVEF) and the severity of exercise-induced ischaemia, 20 patients with stable coronary artery disease (CAD) underwent radionuclide ventriculography during mental stress testing and stress myocardial perfusion single-photon emission tomography (SPET). We also examined whether changes in haemodynamic and neurohormonal parameters are related to changes in LVEF during mental stress. The LVEF decreased from 54.8%±17.7% to 49.8%±16.2% with mental stress (P<0.0005). Ten of the 20 patients (50.0%) had a ≥5% decrease in LVEF. The remaining ten patients had no or a <5% decrease in LVEF. There was a significant correlation between the change in LVEF during mental stress and the size of the reversible defect on stress myocardial perfusion SPET (r=-0.80, P<0.0005), with close regional correspondence (75% identical). This correlation was less strong in the 12 patients with a total defect score at rest of <10 (r=-0.69, P=0.014) than in the eight patients with a total defect score at rest of ≥10 (r=-0.94, P=0.001). The changes in blood pressure and heart rate were not significantly correlated with the change in LVEF, but the percent change in adrenaline concentration correlated with the change in LVEF. It is suggested that mental stress impairs systolic function by inducing transient myocardial ischaemia. The effect of neurohormonal responses during mental stress on LV systolic function may also be important in patients with CAD.
Circulation, Apr 25, 2006
Hypertension Research, 2011
Hypertension Research, 2008
Antihypertensive therapy has been well established to reduce hypertension-related morbidity and m... more Antihypertensive therapy has been well established to reduce hypertension-related morbidity and mortality, but the optimal therapy for Japanese patients remains unknown. The Valsartan Amlodipine Randomized Trial (VART), a prospective randomized open-label trial, was designed to determine whether treatment with an angiotensin II type 1 receptor blocker (valsartan) or a calcium channel blocker (amlodipine) lowers cardiovascular disease events in essential hypertensives in Japan. Registration, randomization and data entry were performed over the Internet. The minimization method (to control for age, gender, blood pressure level and history) was used at random assignment to ensure that the background factors were equivalent between the groups at baseline. After the registration, patients were followed-up for cardiovascular events (primary endpoints), echocardiography, 123 I-metaiodobenzylguanidine (MIBG) imaging, laboratory tests and blood pressure for 3 years. Currently, 797 patients have been enrolled and assigned to two groups: a valsartan (n =399) and an amlodipine (n =398) group. At baseline, controlled factors (age, gender, blood pressure level, and left ventricular hypertrophy) and the proportions of patients with diabetes and hyperlipidemia were equally allocated. At 12 months, both drugs evenly and significantly lowered blood pressure to the target level (valsartan: 133/79 mmHg; amlodipine: 132/79 mmHg). In conclusion, by combining the data on cardiovascular events with the results of echocardiographic, radionuclide imaging, and blood/urine studies, the VART study will provide mechanistic insights into the clinical outcomes and treatment effects of the trial.
Journal of Human Hypertension, Aug 14, 2013
The paper has been retracted due to concerns raised by the publishing institution regarding probl... more The paper has been retracted due to concerns raised by the publishing institution regarding problems with management of conflicts of interest and with the reliability of the published data.
Circulation journal, 2004
hurg-Strauss syndrome (CSS) is characterized by asthma, eosinophilia, and systemic necrotizing va... more hurg-Strauss syndrome (CSS) is characterized by asthma, eosinophilia, and systemic necrotizing vasculitis, and cardiac involvement (ie, eosinophilic heart disease 1,2) is the major cause of morbidity and mortality. 1,3 However, there are no reports of an association between left ventricular dysfunction caused by eosinophilic heart disease and myocardial blood flow or myocardial fatty acid metabolism. We describe a patient with CSS and eosinophilic heart disease that progressed to dilated cardiomyopathy and which exhibited abnormal myocardial fatty acid metabolism on myocardial scintigraphy.
Hypertension Research, 2016
European Heart Journal, 2013
Mineralocorticoid receptor antagonists have been shown to be beneficial in treatment and mortalit... more Mineralocorticoid receptor antagonists have been shown to be beneficial in treatment and mortality reduction in heart failure with reduced ejection fraction in randomized trials. Data regarding their usefulness in HFPEF remains to be studied. We studied the effects of spironolacton (S) on diastolic stiffness and LV remodeling in diabetic pts with HFPEF. Methods: 137 pts 64±12 yrs (56% female) with HFPEF NYHA III with diabetes mellitus and without renal failure were randomized to two groups in order to receive S on top of their treatment (n=68) 25mg/day to further increase to 50mg/day after 8 weeks if no hyperkalemia (>5.5 mmol/l) has been developed or amilorid (A) 2.5 mg/day to increase to 5mg/day after 8 weeks in pts without hyperkalemia (n=69) for 6 months. Medications as ACEI/ARB, β-blockers, loop diuretics were evenly distributed in groups. NTproBNP levels, and diastolic wall stress (DWS) as (PWs-PWd) /PWs, LV mass index (LVMI), septal E/Em, LA volume index (LAVI) were measured by EchoCG by two independent observers unaware of the aim of the study in 1, 30, 90 and 180 days follow up. Results: In 30 days there were no significant changes in all parameters. In 90 day E/Em were significantly less in S compared with A (10.8±2.3 vs 12.1±3.1, p<0.05) without changes in other parameters. This difference remained unchanged throughout the study. In 180 days DWS, LVMI, LAVI and NTproBNP levels were significantly better in S group.
Circulation. Cardiovascular interventions, 2009
Injection of bone marrow mononuclear cells has been reported to promote neovascularization of isc... more Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of ...
Nihon rinsho. Japanese journal of clinical medicine, Jan 28, 2007
Movement Disorders, 2009
Deep brain stimulation (DBS) is successfully used for symptomatic treatment of various movement d... more Deep brain stimulation (DBS) is successfully used for symptomatic treatment of various movement disorders. However, the technique is not without risks for adverse events related to surgery, hardware, or stimulation itself. There is a continued need for standardized reporting of adverse events related to DBS surgery, especially with respect to serious infections. 1 These include the rare complication of intracerebral infections, which if not recognized, may cause serious and longterm morbidity. A 55-year-old man with tremor-predominant Parkinson's disease underwent unilateral DBS surgery. The electrode (3387, Medtronic, Minneapolis, MN) was placed in the right
Journal of the American College of Cardiology, 2004
Noninvasive Imaging sound system. Recent developed real time compound imaging, Sono CT, which sup... more Noninvasive Imaging sound system. Recent developed real time compound imaging, Sono CT, which suppresses the artifacts and reinforces real structures by scanning from different angles and averaging these independent frames, may detect IMT and calcified lesions noninvasively. Methods: We tried to measure IMT and evaluate calcified lesions of distal LAD using Sono CT after guiding usual TTDE (HDI 5000, Philips medical systems) in 33 patients (65.7± 9.3 years old) in whom IVUS catheter could be delivered to distal LAD area near Sono CT probe position on coronary intervention therapy for proximal LAD lesions. According to the usual TTDE probe position where the distal LAD flow was detected, we put the Sono CT probe, and tried to find coronary artery and to measure IMT and evaluate calcified lesions of the coronary artery. We confirmed Sono CT probe position was same as the location where we evaluated using IVUS in the catheter laboratory. Two independent echocardiographic experts analyzed whether IMT and calcified lesions could be detected or not. Results: In all the patients, anterior and posterior coronary artery wall could be detected, and in 21 (64%) among these 33 patients we could measure IMT using Sono CT. IMT of the anterior and posterior wall of the distal LAD were 0.5 ± 0.1mm and 0.4 ± 0.1mm, respectively. There were significant correlation between IMT that were measured by Sono CT and those by IVUS (y = 0.71x + 0.24, r = 0.52, P<0.05). Using Sono CT, the calcified lesions could be found in 3 patients in whom IVUS validated calcified lesion at the same portion of coronary arteries, however, usual TTDE could not detect all these three calcified lesions. Conclusion: IMT and calcified lesions of distal LAD can be assessed noninvasively and accurately using Sono CT.
Journal of the American College of Cardiology, 1997
Objectives. The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled s... more Objectives. The Probucol Angioplasty Restenosis Trial was a prospective, randomized, controlled study that investigated the effectiveness of probucol therapy in reducing the rate of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Background. Antioxidants have an inhibitory effect on smooth muscle cell growth in experiments in vitro and in vivo, which suggests a possible pharmacologic effect on restenosis after PTCA. Methods. One hundred one patients were randomly assigned to receive 1,000 mg/day of probucol or control (no lipid-lowering) therapy 4 weeks before PTCA. After 4 weeks of premedication, both groups underwent PTCA. Probucol was continued until follow-up angiography 24 weeks after PTCA. Angiographic results were analyzed at a core laboratory by quantitative coronary angiography. Results. Dilation was successful in 46 of 50 patients in the probucol group and 45 of 51 in the control group. At follow-up angiography 24 weeks after angioplasty, angiographic restenosis occurred in 9 (23%) of 40 patients in the probucol group and 22 (58%) of 38 in the control group (p ؍ 0.001). Minimal lumen diameter was 1.49 ؎ 0.75 mm (mean ؎ SD) in the probucol group and 1.13 ؎ 0.65 mm in the control group (p ؍ 0.02). Percent diameter stenosis at follow-up angiography in the probucol group was significantly lower than that in the control group (43.9% vs. 56.4%, p ؍ 0.009). The late loss was 0.37 ؎ 0.69 mm in the probucol group and 0.60 ؎ 0.62 mm in the control group (p ؍ 0.13). The loss/gain ratio was 0.32 ؎ 0.74 in the probucol group and 0.56 ؎ 0.81 in the control group (p ؍ 0.059). Net gain was greater in the probucol group than in the control group (0.77 ؎ 0.70 vs. 0.48 ؎ 0.59 mm, p ؍ 0.053). Conclusions. Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.
Journal of the American College of Cardiology, 2002
Background: Second hand smoke (SHS) contributes to endothelial dysfunction. We previously showed ... more Background: Second hand smoke (SHS) contributes to endothelial dysfunction. We previously showed that the angictensin II receptor blocker Iosartan improved endothelial dysfunction and myooadial ischemia. We sought to determine whether Iosartan prevents endothelial dysfunction and myocardial ischemia in rats exposed to SHS. Methods: 84 Sprague-Dawley rats were randomized to receive Iosartan (40 mg/kg/day) and/or SHS (smoking chamber) in a 2 by 2 design. The source of SHS was sidesream smoke of 4 cigarettes every 15 rain, 6 hours a day, 5 days a week. After 6 weeks, the rats were subjected to 17 min of LAD occlusion and 120 rain of reperfusion. In fresh aortic rings precontracted with phenylephrine, endothelium-dependent and-independent relaxation were assessed.Vascular endothelial growth factor (VEGF) in the ischemic myocardium was measured by Western blot analysis. Results: SHS impaired endothelial dependent relaxation to ecetylcholine and endothelial independent relaxation to nitroglycerin. Losartan reduced the impaired maximal vasorelaxation induced by A2.3187. Losarfan increased effective refractory period (ERP) and VF threshold. SHS increased infarct size and VEGF. Losadan decreased infarct size, but did not affect the increased infarct size caused by SHS. Conclusions: SHS impaired endothelial function and increased infarct size and VEGF. Losartan prevented endothelial dysfunction secondary to SHS, but did not affect the increased infarct size caused by SHS.
International Journal of Cardiology, 2007
Background: This study examined feasibility and safety of granulocyte colony-stimulating factor (... more Background: This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI). Methods: Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group (n = 18) or Control group (n = 22). G-CSF treatment was started within 24 h after PCI. 99m Tc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion. Results: LVEF at 6 months was significantly better than that at 4 days in G-CSF group (p = 0.013), but not changed in Control group (p = 0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups. Conclusions: G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.
Hypertension Research, 2001
Hypertension Research, 1992
Hypertension Research, 2008
Antihypertensive therapy has been well established to reduce hypertension-related morbidity and m... more Antihypertensive therapy has been well established to reduce hypertension-related morbidity and mortality, but the optimal therapy for Japanese patients remains unknown. The Valsartan Amlodipine Randomized Trial (VART), a prospective randomized open-label trial, was designed to determine whether treatment with an angiotensin II type 1 receptor blocker (valsartan) or a calcium channel blocker (amlodipine) lowers cardiovascular disease events in essential hypertensives in Japan. Registration, randomization and data entry were performed over the Internet. The minimization method (to control for age, gender, blood pressure level and history) was used at random assignment to ensure that the background factors were equivalent between the groups at baseline. After the registration, patients were followed-up for cardiovascular events (primary endpoints), echocardiography, 123 I-metaiodobenzylguanidine (MIBG) imaging, laboratory tests and blood pressure for 3 years. Currently, 797 patients have been enrolled and assigned to two groups: a valsartan (n =399) and an amlodipine (n =398) group. At baseline, controlled factors (age, gender, blood pressure level, and left ventricular hypertrophy) and the proportions of patients with diabetes and hyperlipidemia were equally allocated. At 12 months, both drugs evenly and significantly lowered blood pressure to the target level (valsartan: 133/79 mmHg; amlodipine: 132/79 mmHg). In conclusion, by combining the data on cardiovascular events with the results of echocardiographic, radionuclide imaging, and blood/urine studies, the VART study will provide mechanistic insights into the clinical outcomes and treatment effects of the trial.
Hypertension, 2000
Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, ... more Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, and abnormal glucose metabolism. However, no study has examined the relative pathological significance of left ventricular hypertrophy and abnormal glucose metabolism on endothelial dysfunction in hypertension. This study was conducted to evaluate whether abnormal glucose tolerance assessed by 75-g oral glucose tolerance test or left ventricular hypertrophy is more closely associated with endothelial dysfunction in never-treated hypertensive patients without elevated fasting blood glucose. We studied 107 unmedicated hypertensive patients (mean age, 54Ϯ10 years) whose fasting blood glucose was Ͻ7.0 mmol/L. Endothelial function was assessed by change in brachial artery diameter in response to reactive hyperemia, and left ventricular mass index was determined by ultrasonography. Simple linear regression analysis demonstrated that endothelial function significantly correlated with left ventricular mass index and 2-hour blood glucose in 75-g oral glucose tolerance test, but not with fasting blood glucose. Multiple linear regression analysis revealed that endothelial function significantly correlated with 2-hour blood glucose (ϭϪ2.68, PϽ0.05) after we controlled for other clinical variables. Patients were divided into 3 groups according to 2-hour blood glucose levels. Endothelial function was more impaired in patients with diabetes (nϭ12; 4.7Ϯ1.8%) and in those with impaired glucose tolerance (nϭ31; 6.3Ϯ2.9%) than in those with normal glucose tolerance (nϭ64; 8.4Ϯ4.5%) (PϽ0.05), but left ventricular mass index was similar in these 3 groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test, rather than left ventricular hypertrophy, may have direct pathophysiological relevance to endothelial dysfunction in borderline to moderate hypertensive patients.
Heart and Vessels, 2010
In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogre... more In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 mumol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% +/- 11% vs 38% +/- 15%, not significant) and 20 mumol/l adenosine diphosphate (48% +/- 13% vs 51% +/- 12%, not significant) between 50 mg clopidogrel and 200 mg ticlopidine. In Japanese patients, there is the possibility that a maintenance dose of 50 mg clopidogrel on platelet inhibition is comparable to 200 mg ticlopidine.
European Journal of Nuclear Medicine, 2000
To evaluate the relationship between the mental stress-induced decrease in left ventricular eject... more To evaluate the relationship between the mental stress-induced decrease in left ventricular ejection fraction (LVEF) and the severity of exercise-induced ischaemia, 20 patients with stable coronary artery disease (CAD) underwent radionuclide ventriculography during mental stress testing and stress myocardial perfusion single-photon emission tomography (SPET). We also examined whether changes in haemodynamic and neurohormonal parameters are related to changes in LVEF during mental stress. The LVEF decreased from 54.8%±17.7% to 49.8%±16.2% with mental stress (P<0.0005). Ten of the 20 patients (50.0%) had a ≥5% decrease in LVEF. The remaining ten patients had no or a <5% decrease in LVEF. There was a significant correlation between the change in LVEF during mental stress and the size of the reversible defect on stress myocardial perfusion SPET (r=-0.80, P<0.0005), with close regional correspondence (75% identical). This correlation was less strong in the 12 patients with a total defect score at rest of <10 (r=-0.69, P=0.014) than in the eight patients with a total defect score at rest of ≥10 (r=-0.94, P=0.001). The changes in blood pressure and heart rate were not significantly correlated with the change in LVEF, but the percent change in adrenaline concentration correlated with the change in LVEF. It is suggested that mental stress impairs systolic function by inducing transient myocardial ischaemia. The effect of neurohormonal responses during mental stress on LV systolic function may also be important in patients with CAD.