Faculty Profiles - MIYOSHI Toru

Papers - MIYOSHI Toru

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Association between coronary artery calcification and left ventricular diastolic dysfunction in elderly people.

Kazuhiro Osawa, Toru Miyoshi, Hiroki Oe, Shuhei Sato, Kazufumi Nakamura, Kunihisa Kohno, Hiroshi Morita, Susumu Kanazawa, Hiroshi Ito

Heart and vessels 31 ( 4 ) 499 - 507 2016.4

Language：English Publishing type：Research paper (scientific journal)

Coronary artery calcification (CAC) is associated with the incidence of congestive heart failure. We evaluated the association between CAC and left ventricular diastolic dysfunction (LVDD) in elderly patients without coronary artery disease. Coronary computed tomography was performed in 1,021 consecutive patients >55 years of age who were suspected of having coronary artery disease. A total of 530 patients (age, 70 ± 8 years; 56 % men) with a LV ejection fraction >50 % and without obstructive coronary artery disease and a history of coronary artery disease were included in the analysis. LVDD was defined according to a standard algorithm by echocardiography (septal e' <8, lateral e' <10, and left atrial volume index ≥34 mL/m(2)). A total of 224 of 530 patients had LVDD. CAC scores in patients with LVDD were higher than those in patients without LVDD (p < 0.01). The prevalence of LVDD in patients with CAC scores ≥400 was greater than that in patients with CAC scores of 0-9 (58 vs. 34 %, p < 0.01). After adjustment for confounding factors, the CAC score was associated with LVDD, with an odds ratio of 1.96 (95 % confidence interval: 1.11-3.43, p = 0.02) for a CAC score ≥400 compared with a CAC score of 0-9. A CAC score ≥400 was associated with LVDD in elderly patients without CAD in this population. Further prospective studies are needed to evaluate the clinical relevance of CAC as a risk of heart failure with preserved ejection fraction.

DOI： 10.1007/s00380-015-0645-5

Gender differences in sensitivity of acetylcholine and ergonovine to coronary spasm provocation test.

Shozo Sueda, Toru Miyoshi, Ysuhiro Sasaki, Tomoki Sakaue, Hirokazu Habara, Hiroaki Kohno

Heart and vessels 31 ( 3 ) 322 - 9 2016.3

Language：English Publishing type：Research paper (scientific journal)

We examined the sex difference concerning the coronary artery response between ACh and ER in this study. We already reported the difference of coronary response between acetylcholine (ACh) and ergonovine (ER). We performed both ACh and ER tests of 461 patients (male 294 patients, female 167 patients, mean age 64.4 ± 11.3 years) during 23 years. Positive coronary spasm was defined as >99 % transient luminal narrowing with usual chest pain and/or ischemic ECG changes. Firstly, ACh was administered in incremental doses of 20/50/(80) μg into the RCA and 20/50/100/(200) μg into the LCA over 20 s. Secondly, ER was administered in a total dose of 40 μg into the RCA and of 64 μg into the LCA over 2-4 min. Intracoronary injection of ACh and ER provoked spasm in 221 patients consisting of 160 male patients and 61 female patients. In female patients, the spasm provoked by ACh was almost perfect except in two patients (59 patients, 96.7 %), while ER provoked spasm in only 20 patients (32.8 %). In male patients, provoked spasm by ACh (129 patients, 80.6 %) was significantly higher than ER (97 patients, 60.6 %). As a spasm provocation test, ACh is more sensitive than ER in both sexes and especially in females. We may select two pharmacological agents by sex differences to provoke coronary artery spasm in the cardiac catheterization laboratory in the future.

DOI： 10.1007/s00380-014-0614-4

Clinical characteristics of responders to treatment with tolvaptan in patients with acute decompensated heart failure: Importance of preserved kidney size. International journal

Hironobu Toda, Kazufumi Nakamura, Makoto Nakahama, Tadashi Wada, Atsuyuki Watanabe, Katsushi Hashimoto, Ritsuko Terasaka, Koji Tokioka, Nobuhiro Nishii, Toru Miyoshi, Kunihisa Kohno, Yusuke Kawai, Kohei Miyaji, Yuji Koide, Motomi Tachibana, Ryo Yoshioka, Hiroshi Ito

Journal of cardiology 67 ( 2 ) 177 - 83 2016.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Recent clinical trials have demonstrated the efficacy of short-term treatment with tolvaptan, an oral vasopressin V2 receptor antagonist, in patients with heart failure. However, the response to tolvaptan varies among patients. The aim of this study was to determine factors associated with response to tolvaptan in patients with acute decompensated heart failure (ADHF). METHODS: The Tolvaptan Registry, a prospective, observational, multicenter cohort study performed in Japan, aims to determine factors affecting the responsiveness of tolvaptan in patients with ADHF. We enrolled ADHF patients treated with tolvaptan and they were divided into two groups: responders and non-responders. Responders were defined as subjects who met all of the following three conditions: (1) increasing urine volume during a 24-hour period after the start of tolvaptan treatment; (2) improvement in New York Heart Association functional class; and (3) decrease in cardiothoracic ratio assessed by chest X-ray on day 3 of tolvaptan administration. RESULTS: Among the 114 patients, treatment with tolvaptan improved three conditions of heart failure in more than half of all the cohorts (71 patients, 62%). As for baseline characteristics, estimated glomerular filtration rate, urine osmolality, and kidney size were significantly greater in responders than in non-responders. Multivariate logistic analysis revealed that kidney size was independently associated with responders (odds ratio: 1.083, p=0.001, 95% confidence interval 1.031-1.137). CONCLUSIONS: The main clinical characteristic of responders to treatment with tolvaptan is that kidney size is preserved.

DOI： 10.1016/j.jjcc.2015.04.017

Complete definite positive spasm on acetylcholine spasm provocation tests: comparison of clinical positive spasm.

Shozo Sueda, Toru Miyoshi, Yasuhiro Sasaki, Kousei Ohshima, Tomoki Sakaue, Hirokazu Habara, Hiroaki Kohno

Heart and vessels 31 ( 2 ) 143 - 51 2016.2

Language：English Publishing type：Research paper (scientific journal)

In the clinical grounds, patients with ≥90 % luminal narrowing during acetylcholine (ACh) testing had variable response. We investigated ischemic findings and chest symptoms in patients with ≥90 % luminal narrowing when performing ACh tests, retrospectively. We performed 763 ACh tests over 13 years (2001-2013). We analyzed chest symptoms and positive ischemic ECG changes during ACh tests. More than 90 % luminal narrowing was found in 441 patients (57.8 %) including 355 patients in the right coronary artery (RCA) and 363 patients in the left coronary artery (LCA). Chest symptom was observed in 386 patients (87.5 %) including 293 patients in the RCA and 304 patients in the LCA. ST elevation was found in 161 patients including 110 in the RCA and 85 patients in the LCA, while ST depression was recognized in 146 patients including 119 patients in the RCA and 117 patients in the LCA. Three quarter of patients with ≥90 % luminal narrowing had significant ischemic ECG changes, whereas two-third of patients with ≥90 % luminal narrowing complained usual chest pain accompanied with significant ischemic ECG changes. Unusual chest symptom was complained in 7.3 % patients with ≥90 % luminal narrowing. Neither chest symptom nor ECG changes were found in 30 patients (6.8 %) with ≥90 % luminal narrowing. A third of these patients had ischemic findings on non-invasive tests before catheterization and six patients had subtotal or total occlusion. We should realize some limitation to define positive coronary spasm based on the ischemic ECG change and chest symptom during ACh tests.

DOI： 10.1007/s00380-014-0595-3

Safety and optimal protocol of provocation test for diagnosis of multivessel coronary spasm.

Shozo Sueda, Toru Miyoshi, Yasuhiro Sasaki, Tomoki Sakaue, Hirokazu Habara, Hiroaki Kohno

Heart and vessels 31 ( 2 ) 137 - 42 2016.2

Language：English Publishing type：Research paper (scientific journal)

We examined the safety of acetylcholine (ACh) and ergonovine (ER) tests retrospectively and investigated the optimal protocol of provocation test for diagnosis of multivessel coronary spasm. We performed 1546 ACh tests and 1114 ER tests during 23 years. ACh was injected in incremental doses of 20/50/80 μg into the right coronary artery (RCA) and of 20/50/100/200 μg into the left coronary artery (LCA) over 20 s. ER was administered in total doses of 40 μg into the RCA and of 64 μg into the LCA over 2-4 min. When a coronary spasm was induced and did not resolve spontaneously within 3 min after the completion of ACh/ER injection, or when hemodynamic instability due to coronary spasms occurred, 2.5-5.0 mg of nitrate was administered into the responsible vessel. To relive provoked spasm, it is necessary to administer nitrate in 31 cases by ACh and in 76 cases by ER (2.0 vs. 6.8 %, p < 0.01) before another vessel attempts. Multivessel spasms were often observed in LCA testing than in RCA testing on both agents [ACh: 78.6 % (11/14) vs. 11.8 % (2/17), p < 0.001, ER: 37.8 % (14/37) vs. 20.5 % (8/39), ns]. Even after the administration of nitrates, positive coronary spasm was obtained in 21.1 % by ACh and 52.9 % by ER tests on another coronary artery. No irreversible complications were recognized on both tests. We should firstly perform spasm provocation tests in the LCA and we may be able to diagnose another vessel spasm by performing the complete spasm provocation tests after the administration of nitrates to relieve provoked spasm in the first attempt.

DOI： 10.1007/s00380-014-0591-7

Contrast-enhanced ultrasound for the evaluation of acute renal infarction.

Toru Miyoshi, Hideki Okayama, Go Hiasa, Yoshitaka Kawata, Tadakatsu Yamada, Yukio Kazatani

Journal of medical ultrasonics (2001) 43 ( 1 ) 141 - 3 2016.1

Language：English Publishing type：Research paper (scientific journal)

A 65-year-old male in the dilated phase of hypertrophic cardiomyopathy and with persistent atrial fibrillation was admitted to our hospital because of an episode of ventricular fibrillation following an appropriate shock from an implantable cardiac defibrillator (ICD). At admission, electrocardiography showed a normal sinus rhythm. He had complained of back pain 7 days after the ICD shock. Renal infarction was suspected, although computed tomography and magnetic resonance imaging could not be performed because of chronic renal failure and the presence of his ICD. We, therefore, used contrast-enhanced ultrasonography with a contrast agent to evaluate his acute kidney injury. This showed the left kidney contained a wedge-shaped area that was not enhanced by the contrast agent, indicating an area of infarction.

DOI： 10.1007/s10396-015-0655-z

Diagnostic Performance of First-Pass Myocardial Perfusion Imaging without Stress with Computed Tomography (CT) Compared with Coronary CT Angiography Alone, with Fractional Flow Reserve as the Reference Standard. International journal

Kazuhiro Osawa, Toru Miyoshi, Takashi Miki, Yasushi Koyama, Shuhei Sato, Susumu Kanazawa, Hiroshi Ito

PloS one 11 ( 2 ) e0149170 2016

Language：English Publishing type：Research paper (scientific journal)

Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first-pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first-pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull's eye map. Invasive FFR <0.8 was considered as positive. On per-vessel analysis, the area under the receiver operating characteristic curve for CCTA plus first-pass CT-MPI and CCTA alone was 0.81 (0.73-0.90) and 0.70 (0.61-0.81), respectively (P = 0.036). CCTA plus first-pass CT-MPI without stress showed 0.73 sensitivity, 0.74 specificity, 0.53 positive predictive value, and 0.87 negative predictive value for detecting hemodynamically significant coronary stenosis. First-pass CT-MPI without stress correctly reclassified 38% of CCTA false-positive vessels as true negative. First-pass CT-MPI without stress combined with CCTA demonstrated excellent diagnostic accuracy, compared with invasive FFR as the reference standard. This technique could complement CCTA for diagnosis of coronary artery disease.

DOI： 10.1371/journal.pone.0149170

A calcified amorphous tumor that developed on both sides of the atrioventricular valve annulus.

Masaki Kinoshita, Hideki Okayama, Go Kawamura, Tatsuya Shigematsu, Tatsunori Takahashi, Toru Miyoshi, Akinori Higaki, Kayo Hara, Yoshitaka Kawata, Go Hiasa, Tadakatsu Yamada, Yukio Kazatani, Yutaka Hayashi

Journal of echocardiography 13 ( 4 ) 148 - 50 2015.12

Language：English Publishing type：Research paper (scientific journal)

We report a rare case of a hemodialysis patient with a calcified amorphous tumor (CAT) on both sides of the atrioventricular valve annulus. A 70-year-old female who had received hemodialysis for 23 years because of chronic glomerulonephritis presented to our hospital with acute heart failure. Echocardiography indicated the presence of mobile cardiac masses on the mitral valve and tricuspid valve annulus. We suspected the presence of a cardiac tumor or vegetation. The patient received 3 g/day sulbactam-ampicillin and 60 mg/day gentamicin. Surgery was performed on the 14th day after hospital admission. The patient underwent mitral valve replacement, tricuspid annuloplasty, and tumor resection. Based on the pathological findings, the cardiac tumor was diagnosed as a CAT.

DOI： 10.1007/s12574-015-0267-z

Maximal acetylcholine dose of 200 μg into the left coronary artery as a spasm provocation test: comparison with 100 μg of acetylcholine.

Shozo Sueda, Hiroaki Kohno, Toru Miyoshi, Tomoki Sakaue, Yasuhiro Sasaki, Hirokazu Habara

Heart and vessels 30 ( 6 ) 771 - 8 2015.11

Language：English Publishing type：Research paper (scientific journal)

As a spasm provocation test of acetylcholine (ACH), incremental dose up (20/50/100 μg) into the left coronary artery (LCA) is recommended in the guidelines established by Japanese Circulation Society. Recently, Ong et al. reported the ACOVA study which maximal ACH dose was 200 μg in the LCA. We compared the angiographic findings between ACH 100 μg and ACH 200 μg in the LCA and also examined the usefulness and safety of ACH 200 μg in Japanese patients without variant angina. As a spasm provocation test, we performed intracoronary injection of ACH 200 μg after ACH 100 μg in 88 patients (55 males, 68.4 ± 11.7 years old) including 59 ischemic heart disease (IHD) patients and 29 non-IHD patients. Positive spasm was defined as >99 % transient stenosis (focal spasm) or 90 % severe diffuse vasoconstriction (diffuse spasm). Positive spasm by ACH 200 μg was significantly higher than that by ACH 100 μg (36 pts: 40.9 % vs. 17 pts: 19.3 %, p < 0.01). Diffuse distal spasm on the left anterior descending artery was more recognized in ACH 200 μg than in ACH 100 μg (30.7 vs. 13.6 %, p < 0.01). In 29 rest angina patients, positive spasm by ACH 200 μg (19 pts) was significantly higher than that by ACH 100 μg (7 pts) (65.5 vs. 24.1 %, p < 0.01). No serious irreversible complications were found during ACH 200 μg. Administration of ACH 200 μg into the LCA was safe and useful. We may reexamine the maximal ACH dose into the LCA.

DOI： 10.1007/s00380-014-0563-y

Prognostic significance of endothelial dysfunction in patients undergoing percutaneous coronary intervention in the era of drug-eluting stents. International journal

Motoki Kubo, Toru Miyoshi, Hiroki Oe, Yuko Ohno, Kazufumi Nakamura, Hiroshi Ito

BMC cardiovascular disorders 15 102 - 102 2015.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Endothelial function is a prognostic predictor in patients undergoing percutaneous coronary intervention (PCI). However, in an era with widespread use of drug-eluting stents, the clinical relevance of endothelial dysfunction on restenosis in patients undergoing PCI has not been fully evaluated. METHODS: This study included 80 patients with stable angina pectoris. Flow-mediated dilation (FMD) of the brachial artery was examined 1 week after PCI. Patients were retrospectively followed-up for an average of 21 months after PCI. The primary endpoints included cardiac death, nonfatal myocardial infarction, stroke, coronary revascularization, and critical limb ischemia. RESULTS: A drug-eluting stent was used in 58 patients and a cardiovascular event was recorded in 34 patients during follow-up. The incidence of all cardiovascular diseases was significantly greater in the low FMD (median FMD <4.2%) than the high FMD (median FMD ≥4.2%) group (60% vs. 25%, p <0.01). Furthermore, the incidence of coronary revascularization was significantly higher in the low than the high FMD group (p = 0.02), while the incidence of in-stent restenosis did not differ between the two groups. Cox regression analysis showed that low FMD was an independent predictor of cardiovascular events (hazard ratio: 2.77, 95% confidence interval: 1.23 to 6.19, p = 0.01). CONCLUSIONS: Impaired brachial artery FMD independently predicts long-term cardiovascular events after PCI in the era of drug-eluting stents.

DOI： 10.1186/s12872-015-0096-z

Influence of Coronary Calcification on the Diagnostic Performance of CT Angiography Derived FFR in Coronary Artery Disease: A Substudy of the NXT Trial. International journal

Bjarne L Nørgaard, Sara Gaur, Jonathon Leipsic, Hiroshi Ito, Toru Miyoshi, Seung-Jung Park, Ligita Zvaigzne, Nikolaos Tzemos, Jesper M Jensen, Nicolaj Hansson, Brian Ko, Hiram Bezerra, Evald H Christiansen, Anne Kaltoft, Jens F Lassen, Hans Erik Bøtker, Stephan Achenbach

JACC. Cardiovascular imaging 8 ( 9 ) 1045 - 1055 2015.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: The goal of this study was to examine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) in relation to coronary calcification severity. BACKGROUND: FFRCT has shown promising results in identifying lesion-specific ischemia. The extent to which the severity of coronary calcification affects the diagnostic performance of FFRCT is not known. METHODS: Coronary calcification was assessed by using the Agatston score (AS) in 214 patients suspected of having coronary artery disease who underwent coronary CTA, FFRCT, and FFR (FFR examination was performed in 333 vessels). The diagnostic performance of FFRCT (≤0.80) in identifying vessel-specific ischemia (FFR ≤0.80) was investigated across AS quartiles (Q1 to Q4) and for discrimination of ischemia in patients and vessels with a low-mid AS (Q1 to Q3) versus a high AS (Q4). Coronary CTA stenosis was defined as lumen reduction >50%. RESULTS: Mean ± SD per-patient and per-vessel AS were 302 ± 468 (range 0 to 3,599) and 95 ± 172 (range 0 to 1,703), respectively. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of FFRCT across AS quartiles. Discrimination of ischemia by FFRCT was high in patients with a high AS (416 to 3,599) and a low-mid AS (0 to 415), with no difference in area under the receiver-operating characteristic curve (AUC) (0.86 [95% confidence interval (CI): 0.76 to 0.96] vs. 0.92 [95% CI: 0.88 to 0.96]) (p = 0.45). Similarly, discrimination of ischemia by FFRCT was high in vessels with a high AS (121 to 1,703) and a low-mid AS (0 to 120) (AUC: 0.91 [95% CI: 0.85 to 0.97] vs. 0.95 [95% CI: 0.91 to 0.98]; p = 0.65). Diagnostic accuracy and specificity of FFRCT were significantly higher than for stenosis assessment in each AS quartile at the per-patient (p < 0.001) and per-vessel (p < 0.05) level with similar sensitivity. In vessels with a high AS, FFRCT exhibited improved discrimination of ischemia compared with coronary CTA alone (AUC: 0.91 vs. 0.71; p = 0.004), whereas on a per-patient level, the difference did not reach statistical significance (AUC: 0.86 vs. 0.72; p = 0.09). CONCLUSIONS: FFRCT provided high and superior diagnostic performance compared with coronary CTA interpretation alone in patients and vessels with a high AS.

DOI： 10.1016/j.jcmg.2015.06.003

Sequential spasm provocation tests might overcome a limitation of the standard spasm provocation tests. International journal

Shozo Sueda, Toru Miyoshi, Yasuhiro Sasaki, Tomoki Sakaue, Hirokazu Habara, Hiroaki Kohno

Coronary artery disease 26 ( 6 ) 490 - 4 2015.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: We examined the clinical usefulness of sequential spasm provocation tests as follows: first, acetylcholine (ACh) test, second, ergonovine (ER) test, and finally, the ACh test following the ER test. PATIENTS AND METHODS: We performed the ACh and ER tests in 461 patients (294 men, 64.4±11.3 years of age) during a 23-year period. In addition, we administered an intracoronary injection of ACh after the ER tests in 240 patients. First, ACh [right coronary artery (RCA): 20/50/(80) μg, left coronary artery (LCA): 20/50/100/(200) μg] was administered incrementally over 20 s. Second, ER (RCA: 40 μg, LCA: 64 μg) was administered over 2-4 min. If a provoked spasm did not occur, we administered an intracoronary injection of ACh (50/80 μg into the RCA and 100/200 μg into the LCA) just after the ER tests. A positive spasm was defined as more than 99% transient luminal narrowing. RESULTS: A positive spasm was observed in 221 (47.9%) patients including 181 ACh-positive (39.3%) and 119 ER-positive (25.8%) patients by the ACh or ER tests. In the 240 patients with a negative spasm in the ACh and ER tests, 48 (10.4%) patients developed provoked spasms on adding ACh after the ER test. The distributions of various cardiac disorders and provoked spasm vessels were similar among the three positive groups. Focal spasm was frequently observed in the ER-positive group, whereas diffuse spasm was frequently obtained in the ACh-positive group and by adding ACh after ER in the positive group. No major complications were recognized during the sequential spasm provocation tests. CONCLUSION: Sequential spasm provocation tests might overcome a limitation of standard spasm provocation tests.

DOI： 10.1097/MCA.0000000000000267

Comprehensive assessment of morphology and severity of atrial septal defects in adults by CT

Kazuhiro Osawa, Toru Miyoshi, Yusuke Morimitsu, Teiji Akagi, Hiroki Oe, Koji Nakagawa, Yoichi Takaya, Yasufumi Kijima, Shuhei Sato, Susumu Kanazawa, Hiroshi Ito

Journal of Cardiovascular Computed Tomography 9 ( 4 ) 354 - 361 2015.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Inc.

Background: Cardiac CT is an excellent tool for evaluating the anatomy of a secundum atrial septal defect (ASD). However, a comprehensive assessment of its usefulness, including measurement of the pulmonary to systemic blood flow ratio in secundum ASD patients, has not been performed. Objective: Therefore, this study was designed to evaluate the usefulness of CT for assessing the hemodynamics of secundum ASD in adults compared with transesophageal echocardiography (TEE), transthoracic echocardiography, and invasive catheterization. Methods: Fifty adult patients with secundum ASD were enrolled. Cardiac CT scans (128-slice multidetector CT instrument) were acquired. These were followed by 2-dimensional reconstruction of the secundum ASDs to determine the defect size, the rim length between the outer edge of the defect, and the pulmonary to systemic blood flow (Qp/Qs) ratio. Results: The maximum sizes of the secundum ASDs derived from CT and TEE studies were comparable (21.2 ± 8.0 vs 20.0 ± 7.3 mm
P = .41
r = 0.960
P &lt
.001). The rim lengths for the aortic, mitral, and tricuspid valves
the inferior vena cava
and posterior atrium were also comparable between CT and TEE measurements. The mean Qp/Qs ratio that was derived from CT measurements was comparable with that found by invasive catheterization (2.3 ± 0.7 vs 2.3 ± 0.8
P = .73
r = 0.786
P &lt
.001). Conclusion: Cardiac CT is feasible for assessing pathology and the severity of secundum ASD in adults.

DOI： 10.1016/j.jcct.2015.04.007

Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial. International journal

Hiroki Oe, Kazufumi Nakamura, Hajime Kihara, Kenei Shimada, Shota Fukuda, Tsutomu Takagi, Toru Miyoshi, Kumiko Hirata, Junichi Yoshikawa, Hiroshi Ito

Cardiovascular diabetology 14 83 - 83 2015.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes. METHODS: We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers. RESULTS: The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups. CONCLUSIONS: Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes. TRIAL REGISTRATION: Registered at http://www.umin.ac.jp under UMIN000003784.

DOI： 10.1186/s12933-015-0242-z

Impact of Ezetimibe Alone or in Addition to a Statin on Plasma PCSK9 Concentrations in Patients with Type 2 Diabetes and Hypercholesterolemia: A Pilot Study. International journal

Toru Miyoshi, Keigo Nakamura, Masayuki Doi, Hiroshi Ito

American journal of cardiovascular drugs : drugs, devices, and other interventions 15 ( 3 ) 213 - 9 2015.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIM: The increase in proprotein convertase subtilisin/kexin type 9 (PCSK9) leads to low-density lipoprotein (LDL) receptor degradation. Statins significantly reduce LDL-cholesterol levels, but upregulate PCSK9. This study evaluated the effect of ezetimibe monotherapy or ezetimibe in combination with a statin on serum levels of PCSK9 in patients with type 2 diabetes and hypercholesterolemia. METHODS: Ezetimibe treatment was given to ten patients with diabetes without statin therapy and ten patients with statin therapy. Plasma levels of PCSK9 were examined at baseline and 24 weeks after treatment. RESULTS: At baseline, PCSK9 concentrations in patients with statin therapy were significantly higher than those in patients without statin use and in control subjects [median (25th-75th percentile) 411 (272-467) and 382 (356-453) ng/mL, respectively, p < 0.01]. After ezetimibe treatment for 24 weeks, LDL-cholesterol, triglyceride and remnant-like lipoprotein cholesterol were significantly decreased in both groups. However, PCSK9 concentration did not change compared with baseline measurements in both groups. The percentage change in LDL-cholesterol after ezetimibe therapy for 24 weeks was not correlated with the percentage change in PCSK9 concentration. CONCLUSION: Ezetimibe may reduce LDL-cholesterol levels without affecting PCSK9 in patients with type 2 diabetes and hypercholesterolemia.

DOI： 10.1007/s40256-015-0119-2

Remote ischemic preconditioning reduces contrast-induced acute kidney injury in patients with ST-elevation myocardial infarction: a randomized controlled trial. International journal

Toshiaki Yamanaka, Yusuke Kawai, Toru Miyoshi, Tsutomu Mima, Kenji Takagaki, Saori Tsukuda, Yukio Kazatani, Kazufumi Nakamura, Hiroshi Ito

International journal of cardiology 178 136 - 41 2015.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Contrast medium-induced acute kidney injury (CI-AKI) is a cardiovascular complication after myocardial infarction treated with emergency percutaneous coronary intervention. The aim of this randomized, sham-controlled trial was to evaluate the impact of remote ischemic preconditioning (RIPC) on CI-AKI in patients with ST-elevation myocardial infarction who received emergency primary percutaneous coronary intervention. METHODS AND RESULTS: Patients with a suspected ST-elevation myocardial infarction were randomly assigned at a 1:1 ratio to receive percutaneous coronary intervention either with (n=63) or without (n=62) RIPC (intermittent arm ischemia through three cycles of 5min of inflation and 5min of deflation of a blood pressure cuff). A total of 47 RIPC patients and 47 control patients met all study criteria. The primary endpoint was the incidence of CI-AKI, which was defined as an increase in serum creatinine >0.5mg/dL or >25% over the baseline value 48-72h after administration of contrast medium. The incidence of CI-AKI was 10% (n=5) in the RIPC group and 36% (n=17) in the control group (p=0.003). The odds ratio of CI-AKI in patients who received RIPC was 0.18 (95% confidence interval: 0.05-0.64; p=0.008). CONCLUSIONS: In patients with ST-elevation myocardial infarction, RIPC before percutaneous coronary intervention reduced the incidence of CI-AKI.

DOI： 10.1016/j.ijcard.2014.10.135

Single administration of vildagliptin attenuates postprandial hypertriglyceridemia and endothelial dysfunction in normoglycemic individuals. International journal

Kaoru Noguchi, Minoru Hirota, Toru Miyoshi, Yoshinori Tani, Yoko Noda, Hiroshi Ito, Seiji Nanba

Experimental and therapeutic medicine 9 ( 1 ) 84 - 88 2015.1

Language：English Publishing type：Research paper (scientific journal)

Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the development of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl peptidase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow-mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantly suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No significant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vildagliptin may be a promising antiatherogenic agent.

成人先天性心疾患センター開設と教育体制の確立

赤木禎治, 中川晃志, 高谷陽一, 三好亨, 西井伸洋, 大月審一, 笠原慎吾, 佐野俊二, 伊藤浩

日本成人先天性心疾患学会雑誌 4 ( 1 ) 110 - 110 2015.1

Nonalcoholic Hepatic Steatosis Is a Strong Predictor of High-Risk Coronary-Artery Plaques as Determined by Multidetector CT. International journal

Kazuhiro Osawa, Toru Miyoshi, Kentarou Yamauchi, Yasushi Koyama, Kazufumi Nakamura, Shuhei Sato, Susumu Kanazawa, Hiroshi Ito

PloS one 10 ( 6 ) e0131138 2015

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT). METHODS: This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification. RESULTS: Compared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (≥86 cm2; 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94-9.07, p<0.01). CONCLUSIONS: Diagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.

DOI： 10.1371/journal.pone.0131138

Non-invasive computed fractional flow reserve from computed tomography (CT) for diagnosing coronary artery disease – Japanese results from NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps).

Toru Miyoshi, Kazuhiro Osawa, Hiroshi Ito, Susumu Kanazawa, Takeshi Kimura, Hiroki Shiomi, Sachio Kuribayashi, Masahiro Jinzaki, Akio Kawamura, Hiram Bezerra, Stephan Achenbach, Bjarne L Nørgaard

Circulation journal : official journal of the Japanese Circulation Society 79 ( 2 ) 406 - 12 2015

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Recently, a non-invasive method using computational fluid dynamics to calculate vessel-specific fractional flow reserve (FFRCT) from routinely acquired coronary computed tomography angiography (CTA) was described. The Analysis of Coronary Blood Flow Using CT Angiography: Next Steps (NXT) trial, which was a prospective, multicenter trial including 254 patients with suspected coronary artery disease, noted high diagnostic performance of FFRCT compared with invasive FFR. The aim of this post-hoc analysis was to assess the diagnostic performance of non-invasive FFRCT vs. standard stenosis quantification on coronary CTA in the Japanese subset of the NXT trial. METHODS AND RESULTS: A total of 57 Japanese participants were included from Okayama University (n=36), Kyoto University (n=17), and Keio University (n=4) Hospitals. Per-patient diagnostic accuracy of FFRCT(74%; 95% confidence interval [CI]: 60-85%) was higher than for coronary CTA (47%; 95% CI: 34-61%, P<0.001) arising from improved specificity (63% vs. 27%, P<0.001). FFRCT correctly reclassified 53% of patients and 63% of vessels with coronary CTA false positives as true negatives. When patients with Agatston score >1,000 were excluded, per-patient accuracy of FFRCT was 83% with a high specificity of 76%, similar to the overall NXT trial findings. CONCLUSIONS: FFRCT has high diagnostic performance compared with invasive FFR in the Japanese subset of patients in the NXT trial.

DOI： 10.1253/circj.CJ-14-1051

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