Validation of a Five-Year Prognostic Model Using 123I-metaiodobenzylguanidine Scintigraphy in Patients with Heart Failure.

Background: 123I-metaiodobenzylguanidine (MIBG) scintigraphy evaluates the severity and prognosis of patients with heart failure. A prognostic model has been proposed using a multicenter study data of 123I-MIBG scintigraphy. We evaluated the usefulness of the model using a database. Methods: The study included 208 patients with noncompensated heart failure requiring hospitalization. 123I-MIBG scintigraphy and echocardiography were performed predischarge and 6 months postdischarge. The 5-year mortality rate was calculated by the model and classified into tertiles. Results: In 208 patients, 56 cardiac deaths occurred within the observation period (median, 4.83 years). In the evaluation of predischarge parameters, the predicted 5-year mortality was 15.5% ± 5.0%, 33.5% ± 3.9%, and 51.2% ± 8.2%, and 11 (16.2%), 18 (27.3%), and 27 (36.5%) cardiac deaths occurred in groups 1, 2, and 3, respectively. At the 6-month postdischarge evaluation, the estimated mortality was 8.2% ± 2.2%, 18.5% ± 4.8%, and 43.0% ± 12.1%, and 6 (9.4%), 21 (29.2%), and 29 (40.3%) cardiac deaths occurred, respectively. The predischarge Kaplan-Meier survival analysis showed significant difference between groups 1 and 3 (P value 0.014). Moreover, the 6-month postdischarge evaluation showed significant difference between group 1 and 2, and between groups 1 and 3 (P value 0.016, <0.001, respectively). For groups 1 and 3, the 6-month postdischarge difference was more significant than the predischarge difference (Chi-square 16.7 and 8.1, respectively). Conclusions: The prognostic model using 123I-MIBG scintigraphy was useful in predicting mortality risk in patients with heart failure. The estimated mortality at 6 months postdischarge was more useful than the predischarge estimation for heart failure hospitalization.

Novel pathological implications of serum uric acid with cardiovascular disease risk in obesity.

AIMS: This cohort study intended to elucidate the association between serum uric acid (SUA) levels and cardiovascular disease events in Japanese patients with obesity. METHODS: Altogether, 450 obese Japanese outpatients were enrolled in a multicenter prospective cohort Japan, the Japan Obesity and Metabolic Syndrome Study. Primary analysis regarding the measurements of cardiovascular risk factors, including SUA levels, and the occurrence of macrovascular complications was based on following the participants over a 5-year period. RESULTS: Of the eligible patients, 335 (74.4%) were followed into the fifth year. During the study period, 15 coronary heart disease, 7 stroke, and 6 arteriosclerosis obliterans events occurred in 39 patients. The CVD incidence rate was 15.8 per 1000 person-years. In the analysis of adjusted models for traditional risk factors, hyperuricemia was a significant factor for the incidence of CVD events, especially in female obese patients. Additionally, we estimated the association between SUA levels and CVD events using cubic spline models, which showed a U-shaped association in both male and female patients. CONCLUSIONS: SUA is an effective predictor of CVD events in female obese patients and a risk factor for CVD incident in obese patients.

Study protocol for assessment of the coagulation potential of concomitantly used factor VIII concentrates in patients with haemophilia A with emicizumab prophylaxis (CAGUYAMA Study): a multicentre open-label non-randomised clinical trial.

INTRODUCTION: Emicizumab prophylaxis substantially reduces bleeding episodes in patients with haemophilia A (HA). The haemostatic efficacy of emicizumab in patients with HA is estimated as approximately 15% based on mimic activity of factor (F) VIII. Although it has been proven effective in preventing bleeding, its haemostatic effect during breakthrough bleeding or surgery is considered insufficient. Therefore, haemostatic management of emicizumab-treated patients with HA without inhibitors frequently requires FVIII replacement therapy. In haemostatic management of emicizumab-treated patients with HA, conventional FVIII dosage calculations are used in clinical practice without considering the coagulant effects of emicizumab. METHODS AND ANALYSIS: In the CAGUYAMA study, 100 patients with HA without inhibitors will be enrolled for a maximum duration of 1 year, and samples of 30 events following the concomitant use of FVIII concentrates (30±5 U/kg) with emicizumab will be collected. An 'event' is defined as obtaining blood samples at preadministration and postadministration of FVIII concentrates during a breakthrough bleeding or a surgical procedure. Global coagulation assays will be used to measure the coagulation potential of the obtained samples. Clot waveform analysis (CWA) is used to identify the primary end-point, that is, the degree of improvement in the maximum coagulation rate at preadministration and post-administration of fixed-dose FVIII concentrations. The parameter obtained from CWA, which is triggered by an optimally diluted mixture of prothrombin time reagent and activated partial thromboplastin time reagent, is reported to be an excellent marker for assessing the degree of improvement of the coagulation potential in emicizumab-treated plasmas. ETHICS AND DISSEMINATION: The CAGUYAMA study was approved by the Japan-Certified Review Board of Nara Medical University (Approval ID; nara0031). The study results will be communicated through publication in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: jRCTs051210137.

Prevention of Contrast-Induced Nephropathy After Emergency Percutaneous Coronary Intervention With a Single Bolus Administration of High-Concentrate Sodium Bicarbonate　- Rationale and Design of a Single-Arm Study Compared With Historical Controls.

Background: Contrast-induced nephropathy (CIN) is clinically important because of its poor prognosis. The incidence of CIN is higher in emergency than elective percutaneous coronary intervention (PCI) because there is no established method to prevent CIN. The aim of this study is to evaluate whether bolus administration of a concentrated solution of sodium bicarbonate can prevent CIN in patients undergoing emergency PCI. Methods and Results: This multicenter prospective single-arm trial with historical controls will include patients who are aged ≥20 years and will undergo cardiac catheterization for suspected acute myocardial infarction (AMI). Patients will receive an intravenous bolus administration of concentrated sodium bicarbonate solution (7% or 8.4%, 20 mEq) and will be observed for 72±12 h. Data for the control group, comprising all patients who underwent PCI for AMI between January 1, 2020 and December 31, 2020 across participating hospitals, will be extracted. The primary endpoint is the incidence of CIN, defined as an increase in serum creatinine of >0.5 mg/dL or >25% from baseline within 48±12 h. We will evaluate the endpoints in the prospective group and compare them with those in the historical control group. Conclusions: This study will evaluate whether a single bolus administration of concentrated sodium bicarbonate can prevent CIN after emergency PCI.

Feasibility and acceptability of novel functional electronic stimulated rehabilitation application for treatment in patients with cerebrovascular disorders: the FRAT study protocol.

BACKGROUND: The prognosis of patients with cerebrovascular disorders is poor owing to their high residual rate of hemiplegia. Delayed withdrawal from synkinesis is a major cause of prolonged hemiplegia; however, effective rehabilitation has not been established. This single-arm, open-label study aims to evaluate the influence of a low-frequency treatment device on canceling synkinesis in patients with incomplete paralysis and cerebrovascular disorders. METHODS: Eligible participants will include patients aged 20 years or older with incomplete paralysis, defined as upper limb Brunnstrom stage (BRS) of 2-4, who are within 1 month of onset of a cerebrovascular disorder. Qualified patients will be assigned to the novel rehabilitation treatment with IVES+ for 4 weeks. The primary endpoint of the study is the change from baseline in the upper-limb Fugl-Meyer Assessment (FMA) 2 weeks after the start of treatment. The secondary endpoints are changes in the amount of Functional Independence Measure, changes in the amount of upper-limb BRS, and changes in the amount of Barthel Index (BI) compared to the pre-intervention value at weeks 2 and 4; changes in the upper-limb FMA scores at 1, 3, and 4 weeks; changes in grip strength compared to the pre-intervention values at 1, 2, 3, and 4 weeks; and changes in upper-limb strength (manual muscle test) compared to the pre-intervention values at 1, 2, 3, and 4 weeks. DISCUSSION: This study will explore the usefulness of IVES+ for recovery from motor paralysis in patients with cerebrovascular disorders. TRIAL REGISTRATION: Japanese Clinical Registry, jRCTs052180226. Date of registration: February 1, 2022.

The Relationship between Tumor Development and Sarcoidosis in Aspects of Carcinogenesis before and after the Onset of Sarcoidosis.

Background and Objectives: It is still unclear whether sarcoidosis is likely to be associated with tumors. In addition, the use of an immune checkpoint inhibitor has been reported to initiate the onset of sarcoidosis. We retrospectively analyzed tumor development before and after the diagnosis of sarcoidosis and examined the impact of having a history of tumors on the activity or the severity of sarcoidosis. Materials and Methods: We recruited 312 consecutive cases of sarcoidosis and analyzed the tumor development before and after the onset of sarcoidosis. Results: Among them, 25 cases were diagnosed with malignant tumor after diagnosis of sarcoidosis. In the analysis of the tumor-development group after diagnosis of sarcoidosis, both serum angiotensin I-converting enzyme and mediastinal lymph node size were significantly reduced at the time of malignant tumor diagnosis compared to at the onset of sarcoidosis, indicating that the decreasing activity of sarcoidosis may be partly associated with tumor development. Furthermore, we examined 34 cases having tumor history before the onset of sarcoidosis and analyzed the effect of tumor history on the severity of sarcoidosis. Cases with a malignant tumor in the past were older and had less complicated organs of sarcoidosis than cases without malignant tumors in the past. Oral corticosteroid therapy was administrated more frequently in cases without malignant tumors in the past, indicating that the history of a malignant tumor may influence the severity of sarcoidosis. Conclusion: These results indicate that tumor development may be partly associated with the activity or severity of sarcoidosis.

Effect of NOciception Level-Directed analgesic management on Opioid usage in Robot-assisted laparoscopic radical prostatectomy (NOLDOR): study protocol for a single-centre single-blinded randomised controlled trial.

Background: The nociception level (NOL) index discriminates noxious stimuli during surgery with high sensitivity and specificity. Although some studies have reported that a NOL-directed opioid protocol reduces intraoperative opioid consumption, one study implied that it might cause an unintended increase in the stress response. Therefore, we designed a study to investigate the effects of the NOL-directed opioid protocol and measure inflammatory biomarkers. Methods: This single-centre RCT will enrol 54 patients undergoing robot-assisted laparoscopic radical prostatectomy. Eligible patients will be randomly allocated to receive (i) NOL-directed intraoperative opioid management (NOL group) or (ii) conventional intraoperative analgesic management (control group). The remifentanil infusion rate will be determined solely using the NOL index during surgery in the NOL group. The primary outcome will be the mean intraoperative remifentanil infusion rate. Secondary outcomes will include the plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein, and cortisol) and the variation in the NOL index at the start of pneumoperitoneum and with postural changes. Conclusions: This study is expected to accumulate evidence on the effects of NOL-directed analgesic opioid protocol and provide additional evidence regarding the variability of stress responses and the character of the NOL index. Clinical trial registration: JRCTs052220034.

Effects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction.

PURPOSE: The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Eighty-four STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients who treated with MRA (N = 42), and those who did not (N = 42). The LV end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography, and plasma procollagen type III amino terminal peptide (PIIINP) was measured before and 3 weeks after treatment. The delayed total defect score (TDS), delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined using 123I-MIBG scintigraphy after 3 weeks. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the MRA group showed significantly lower TDS and WR values (TDS: 22.8 ± 8.1 vs 32.2 ± 11.5, P < 0.005; WR: 31.1 ± 9.0% vs 42.7 ± 9.9%, P < 0.001) and a significantly higher H/M ratio (2.23 ± 0.41 vs 2.03 ± 0.36, P < 0.05) than the non-MRA group. The degree of change in LV parameters, and PIIINP were more favorable in the MRA group than in the non-MRA group. Moreover, multiple linear regression analyses revealed that both WR and not MRA treatment were significant predictor for LV remodeling, along with PIIINP concentrations. CONCLUSION: Administration of eplerenone improves CSNA and prevents LV remodeling in patients with a first STEMI.

Zonisamide for the Efficacy of Sleep Abnormality in Parkinson's Disease (ZEAL Study): A Protocol for Randomized Controlled Trials.

Background: Sleep disorders are one of the most frequent non-motor symptoms of Parkinson's disease (PD), and the efficacy of dopaminergic agents remains controversial. Clinical randomized control trials for the treatment of sleep disorders in PD are limited. Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) improved motor symptoms and wearing-off in patients with PD. Patients with PD were reported to have dream-enacting behavior that was resolved after treatment with zonisamide. This study aimed to verify the safety and efficacy of zonisamide for sleep disorders and rapid eye movement (REM) sleep behavioral disorders using a mobile two-channel electroencephalography (EEG)/electrooculography (EOG) recording system. Methods and Analysis: The present study is a randomized placebo-controlled trial to determine the efficacy of zonisamide for sleep disorders in patients with PD. This study was designed to be single-blind, but the subject allocation is randomized by an independent allocation manager via computer-generated block randomization. The subjects in the treatment group took zonisamide (25 mg per day) before bedtime for 28 days. The sleep index is analyzed using a portable EEG/EOG recording system collected on two consecutive nights within 7 days prior to the intervention and reobtained on one night within 2 days after the 28-day administration of zonisamide. The amount of change in sleep efficiency before and after the 28-day administration will be compared between the zonisamide treatment group and placebo group concerning the primary endpoint. As for the secondary endpoint, the change in the ratio of other sleep parameters, including REM sleep without atonia, or sleep architecture will be evaluated. Ethics and Dissemination: The protocol was approved by the Nara Medical University Certified Review Board (CRB5200002). The trial was notified and registered with the Japan Registry of Clinical Trials (jRCTs051200160). Written informed consent will be obtained from every participant using informed consent approved by the CRB. The results of this trial will be disseminated through peer-reviewed scientific journals.

Comparison of efficacy between dipeptidyl peptidase-4 inhibitor and sodium-glucose cotransporter 2 inhibitor on metabolic risk factors in Japanese patients with type 2 diabetes mellitus: Results from the CANTABILE study.

AIMS: The aim of this study was to compare the effectiveness of teneligliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, at reducing a composite outcome of three metabolic risk factors (obesity, hypertension, and dyslipidemia) in Japanese patients with type 2 diabetes mellitus (T2DM) and metabolic risks. METHODS: In this prospective, multicenter, open-label, randomized, parallel-group comparison study, 162 patients with T2DM and one or more metabolic risk factors were randomized into a teneligliptin or canagliflozin group and treated for 24 weeks. The primary endpoint was the composite percentage of subjects who experienced an improvement in at least one metabolic risk after 24 weeks of treatment. RESULTS: The primary endpoint was achieved significantly by more patients in the canagliflozin group than in the teneligliptin group (62.2% vs. 31.3%, p = 0.0004). A ≥ 3% body weight loss was also achieved by significantly more participants in the canagliflozin group than in the teneligliptin group (55.9% vs. 10.5%, p < 0.0001). CONCLUSIONS: This study showed canagliflozin to be more effective at reducing metabolic risks than teneligliptin. In Japanese patients with T2DM and metabolic risk factors, SGLT2 inhibitors may be superior to DPP-4 inhibitors at controlling multiple metabolic risk.

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor Canagliflozin for Heart Failure With Preserved Ejection Fraction in Patients With Type 2 Diabetes.

Background: The efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. Methods and Results: In a multicenter, controlled trial, the CANONICAL study, we enrolled 82 HFpEF (left ventricular ejection fraction [LVEF] ≥50%) patients with type 2 diabetes (T2D) aged ≥65 years, with plasma B-type natriuretic peptide (BNP) ≥100 pg/mL or plasma N-terminal pro BNP (NT-proBNP) ≥400 pg/mL or history of HF. Patients were randomly assigned to 2 groups and were administered either the SGLT2 inhibitor canagliflozin (100 mg/day) for 24 weeks or standard therapy. The primary endpoints were changes in body weight (BW) and BNP concentrations. Mean (±SD) patient age, body mass index, and LVEF were 75.7±6.5 years, 25.0±3.6 kg/m2 and 61.5±7.6%, respectively. At 24 weeks, BW was significantly lower in the canagliflozin than standard therapy group. The extent of BNP reductions at 4 weeks was significantly greater in the canagliflozin than standard therapy group (P<0.05), but at 24 weeks there was no significant difference between the 2 groups. Conclusions: In this study, canagliflozin treatment reduced BW, but did not significantly reduce plasma BNP concentrations compared with standard therapy after 24 weeks treatment in T2D patients with HFpEF. Further large-scale randomized studies are needed to conclude the beneficial effects of canagliflozin in T2D patients with HFpEF.

Protocol for a Randomized, Crossover Trial to Decrease Time in Hypoglycemia by Combined Intervention of the Usage of Intermittent-Scanning Continuous Glucose Monitoring Device and the Structured Education Regarding its Usage: Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study).

OBJECTIVE: Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG). METHODS: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia ( < 70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, Feb 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals. CONCLUSION: The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM.

Assessment of the accuracy of an intermittent-scanning continuous glucose monitoring device in patients with type 2 diabetes mellitus undergoing hemodialysis (AIDT2H) study.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty-one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P < .01), although the sensor glucose levels were significantly lower than the capillary glucose levels. The accuracy of FreeStyle Libre in patients undergoing HD became deteriorated with the days of usage. The percentage of sensor results in Zones A and B in the consensus error grid analysis and in the Clarke error grid analysis were 99.7% and 99.0%, respectively. Its insufficient accuracy necessitates adjunct usage of FreeStyle Libre with self-monitoring of blood glucose in patients undergoing HD.

Efficacy of Add-on Therapy with Carvedilol and the Direct Renin Inhibitor Aliskiren for Improving Cardiac Sympathetic Nerve Activity, Cardiac Function, Symptoms, Exercise Capacity and Brain Natriuretic Peptide in Patients with Dilated Cardiomyopathy.

Purpose/Method: Aliskiren is a direct renin inhibitor that has been reported to be effective for CHF, but the usefulness of combined therapy with carvedilol and aliskiren has not been reported. Forty-four patients with dilated cardiomyopathy (DCM) were randomized into a group receiving add-on therapy with carvedilol plus aliskiren and another group receiving carvedilol alone for 6 months. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. Cardiac sympathetic nerve activity was evaluated by 123I-MIBG imaging, with the delayed heart-to-mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). Results: Combined add-on therapy with carvedilol and aliskiren improved several parameters much more than carvedilol alone (p<0.05) with respect to TDS, ejection fraction (EF), NYHA, SAS on 6 months and the changes in TDS, EF, end-diastolic volume and brain natriuretic peptide (BNP). Conclusion: Add-on therapy with carvedilol and aliskiren is more effective than carvedilol alone for improving cardiac sympathetic nerve activity, cardiac function, symptoms, exercise capacity, and brain natriuretic peptide in patients with DCM.

A 2-Year Prospective Study on the Differences in Prognostic Factors for Major Adverse Cardiovascular, Cerebrovascular and Renal Events Between Patients with Mild and Severe Chronic Kidney Disease.

Purpose/Method: No studies have reported on prognostic markers in patients with chronic kidney disease (CKD) according to the severity of the disease. Therefore, in this multicenter, prospective trial performed as part of the Gunma CKD SPECT Multicenter Study, we recruited 311 patients with CKD (eGFR < 60 min/mL/1.73 m2) including 50 patients on hemodialysis and followed them for 2 years. The study sample underwent stress 99mTc-tetrofosmin SPECT for suspected or possible ischemic heart disease. We evaluated the summed stress score (SSS), summed rest score (SRS), summed difference score (SDS) and cardiac function with electrocardiogram-gated SPECT. Then, we compared the differences in prognostic markers for major adverse cardiac, cerebrovascular, and renal events (MACCRE) between patients with mild CKD (30 min/mL/1.73 m2 ≤ eGFR <60 min/mL/1.73 m2; n=184) and those with severe CKD (eGFR <30 min/mL/1.73 m2; n=97). Results: Of 281 patients available for analysis, 91 experienced MACCRE. In a multivariate Cox proportional hazards analysis of factors related to MACCRE, in patients with mild CKD the significant prognostic markers were SDS (P=0.002) and end-systolic volume (ESV, P=0.034); and in the patients with severe CKD, they were eGFR (P=0.03) and diabetes-mellitus (DM, P=0.023). Conclusions: Our findings indicate that SDS and ESV are significant prognostic markers for MACCRE in patients with mild CKD and eGFR and DM are significant prognostic markers in patients with severe CKD.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol.

BACKGROUND: Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group. CONCLUSIONS: Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

Rationale, Design, and Methods of the Study of Comparison of Canagliflozin vs. Teneligliptin Against Basic Metabolic Risks in Patients with Type 2 Diabetes Mellitus (CANTABILE study): Protocol for a Randomized, Parallel-Group Comparison Trial.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors are widely used antidiabetic drugs. However, to date, no studies have directly compared the effects of these two drugs on the components of the metabolic syndrome in patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: The Comparison of Canagliflozin vs. Teneligliptin against Basic Metabolic Risks in Patients with T2DM (CANTABILE) study aims to examine whether the DPP-4 inhibitor (teneligliptin) or the SGLT2 inhibitor (canagliflozin) is the more effective drug for reducing metabolic risk factors as a composite in Japanese patients with T2DM. METHODS: The CANTABILE study is a prospective, multicenter, open-label, randomized, parallel-group comparison study. A total of 200 patients with T2DM treated with metformin alone or without glucose-lowering agents will be enrolled if they have one or more of the metabolic risk factors, such as obesity, borderline high blood pressure, and dyslipidemia. They will then will be randomized into the Teneligliptin group or the Canagliflozin group and treated for 24 weeks. The primary endpoint is the composite ratio of subjects with one or more improved metabolic risk factors. The secondary endpoints are the changes in each component of the primary endpoint. PLANNED OUTCOMES: The CANTABILE study provides valuable evidence to indicate the suitability of SGLT2 inhibitors or DPP-4 inhibitors for Japanese patients with T2DM and metabolic risks. TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry number: UMIN000030343. FUNDING: Mitsubishi Tanabe Pharma Corporation.

Most Important Prognostic Values to Predict Major Adverse Cardiovascular, Cerebrovascular, and Renal Events in Patients with Chronic Kidney Disease Including Hemodialysis for 2 Years.

Patients with chronic kidney disease (CKD) have an increased risk of adverse cardiovascular/cerebrovascular events. The aim of this study is to clarify whether stress myocardial perfusion single-photon emission computed tomography (SPECT) could predict cardiovascular/cerebrovascular events. In the Gunma-CKD SPECT Study, a multicenter prospective cohort trial, 311 patients with CKD (estimated glomerular filtration rate < 60 min/mL/1.73 m2) including 50 patients on hemodialysis underwent stress 99mTc-tetrofosmin SPECT for suspected ischemic heart disease and were followed for 2 years. The primary endpoint was the occurrence of cardiac death (CD), while the secondary endpoint was major adverse cardiovascular/cerebrovascular and renal events (MACCRE). MACCRE occurred in 91 out of 286 patients (CD in 13 and other MACCRE in 78 patients). According to a multivariate Cox analysis, hemoglobin (Hb) and end-systolic volume (ESV) were associated with CD (p < 0.05), while the summed difference score, diabetes mellitus (DM), and Hb were associated with MACCRE (p < 0.05). Kaplan-Meier analysis showed that the CD-free rate was higher in patients with ESV < 105 mL (log-rank, p = 0.0013), Hb > 12 g (log-rank, p = 0.0036), and a summed stress score < 6 (log-rank, p = 0.0058). The MACCRE-free rate was higher in patients with SDS = 0 (log-rank, p = 0.0097), without DM (log-rank, p = 0.0091), and with Hb > 12 g (log-rank, p = 0.0023). Myocardial perfusion SPECT parameters as well as renal anemia and DM can be reliable prognostic markers in patients with CKD including hemodialysis.