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.

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.

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.

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.

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity, cardiac function, exercise capacity, and symptom in patients with chronic heart failure and Cheyne-Stokes respiration.

PURPOSE: Adaptive servo-ventilation (ASV) therapy has been reported to be effective for improving central sleep apnea (CSA) and chronic heart failure (CHF). The purpose of this study was to clarify whether ASV is effective for CSA, cardiac sympathetic nerve activity (CSNA), cardiac symptoms/function, and exercise capacity in CHF patients with CSA and Cheyne-Stokes respiration (CSR-CSA). METHODS: In this study, 31 CHF patients with CSR-CSA and a left ventricular ejection fraction (LVEF) ≤ 40% were randomized into an ASV group and a conservative therapy (non-ASV) group for 6 month. 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. CSNA was evaluated by 123I-MIBG imaging, with the delayed heart/mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). RESULTS: The ASV group had significantly better (P < .05) results than the non-ASV group with respect to the changes of AHI (-20.8 ± 14.6 vs -0.5 ± 8.1), TDS (-7.9 ± 4.3 vs 1.4 ± 6.0), and H/M(0.16 ± 0.16 vs -0.04 ± 0.10) on 123I-MIBG imaging, as well as the changes of LVEF (5.3 ± 3.9% vs 0.7 ± 32.6%), SAS (1.6 ± 1.4 vs 0.3 ± 0.7), and NYHA class (2.2 ± 0.4 vs 2.7 ± 0.5) after 6-month therapy. CONCLUSIONS: Performing ASV for 6 months achieved improvement of CSR-CSA, CSNA, cardiac symptoms/function, and exercise capacity in CHF patients with CSR-CSA.

Prognostic value of myocardial perfusion single photon emission computed tomography for major adverse cardiac cerebrovascular and renal events in patients with chronic kidney disease: results from first year of follow-up of the Gunma-CKD SPECT multicenter study.

PURPOSE: Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. We examined whether stress myocardial perfusion single photon emission computed tomography (SPECT) provides reliable prognostic markers for these patients. METHODS: In this multicenter, prospective cohort trial from the Gunma-CKD SPECT study protocol, patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml per 1.73 m(2)] undergoing stress (99m)Tc-tetrofosmin SPECT for suspected or possible ischemic heart disease were initially followed for 1 year, with the following study endpoints: primary, the occurrence of cardiac deaths (CDs), and secondary, major adverse cardiac, cerebrovascular, and renal events (MACCREs). The summed stress score (SSS), summed rest score, and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Left ventricular end-diastolic volume, end-systolic volume (ESV), and ejection fraction were measured using electrocardiogram-gated SPECT. RESULTS: During the first year of follow-up, 69 of 299 patients experienced MACCREs (CD, n = 7; non-fatal myocardial infarction, n = 3; hospitalization for heart failure, n = 13; cerebrovascular accident, n = 1; need for revascularization, n = 38; and renal failure, i.e., hemodialysis initiation, n = 7). ESV and SSS were associated with CDs (p < 0.05), and eGFR and SDS were associated with MACCREs (p < 0.05), in multivariate logistic analysis. Patients with high ESV and high SSS had a significantly higher CD rate during the first year than the other CKD patient subgroups (p < 0.05). Patients with low eGFR and high SDS had a significantly higher MACCRE rate than the other subgroups (p < 0.05). CONCLUSION: Myocardial perfusion SPECT can provide reliable prognostic markers for patients with CKD.

Clinical Feasibility of Simultaneous Acquisition Rest (99m)Tc/Stress (201)Tl Dual-Isotope Myocardial Perfusion Single-Photon Emission Computed Tomography With Semiconductor Camera.

BACKGROUND: The aim of this study was to evaluate the clinical feasibility of simultaneous acquisition of rest (99m)Tc-tetrofosmin/stress (201)Tl dual-isotope single-photon emission computed tomography with a semiconductor gamma camera. METHODS AND RESULTS: Ninety-four patients with known or suspected coronary artery disease (CAD) were enrolled in the study. First, patients were injected with (99m)Tc-tetrofosmin (296 MBq) for rest imaging, followed by (201)Tl (74 MBq) injection during 6 min of vasodilator stress test. Immediately after the stress test, the patients underwent the first electrocardiogram (ECG)-gated simultaneous acquisition including rest and stress perfusion scans. Patients were brought back for the second simultaneous acquisition for the comparison of ECG-gated wall motion between stress and rest scan 30 min later. Coronary angiography was performed in all the patients within 3 months of this protocol. Sensitivity, specificity and accuracy on a per patient basis to detect significant coronary artery stenosis (≥75%) were 88.6%, 79.2% and 86.2%, respectively. Per coronary vessel, sensitivity, specificity and accuracy were as follows: 84.9%, 80.5% and 83% in the left anterior descending coronary artery; 75%, 93.1% and 86.2% in the left circumflex coronary artery; and 74.2%, 85.7% and 81.9% in the right coronary artery. CONCLUSIONS: Simultaneous acquisition of rest (99m)Tc-tetrofosmin/stress (201)Tl dual-isotope protocol had high diagnostic accuracy for significant CAD. (Circ J 2016; 80: 689-695).

Usefulness of Cardiac Sympathetic Nerve Imaging Using (123)Iodine-Metaiodobenzylguanidine Scintigraphy for Predicting Sudden Cardiac Death in Patients With Heart Failure.

The autonomic nervous system plays an important role in the human heart. Activation of the cardiac sympathetic nervous system is a cardinal pathophysiological abnormality associated with the failing human heart. Myocardial imaging using (123)I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, can be used to investigate the activity of norepinephrine, the predominant neurotransmitter of the sympathetic nervous system. Many clinical trials have demonstrated that (123)I-MIBG scintigraphic parameters predict cardiac adverse events, especially sudden cardiac death, in patients with heart failure. In this review, we summarize results from published studies that have focused on the use of cardiac sympathetic nerve imaging using (123)I-MIBG scintigraphy for risk stratification of sudden cardiac death in patients with heart failure.

Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure.

PURPOSE: Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. METHODS: We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. RESULTS: After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. CONCLUSION: Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct.

Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide.

PURPOSE: Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). METHODS: We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. RESULTS: 123I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. CONCLUSION: The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP.

A prediction model for 5-year cardiac mortality in patients with chronic heart failure using ¹²³I-metaiodobenzylguanidine imaging.

PURPOSE: Prediction of mortality risk is important in the management of chronic heart failure (CHF). The aim of this study was to create a prediction model for 5-year cardiac death including assessment of cardiac sympathetic innervation using data from a multicenter cohort study in Japan. METHODS: The original pooled database consisted of cohort studies from six sites in Japan. A total of 933 CHF patients who underwent (123)I-metaiodobenzylguanidine (MIBG) imaging and whose 5-year outcomes were known were selected from this database. The late MIBG heart-to-mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox proportional hazard and logistic regression analyses were used to select appropriate variables for predicting 5-year cardiac mortality. The formula for predicting 5-year mortality was created using a logistic regression model. RESULTS: During the 5-year follow-up, 205 patients (22 %) died of a cardiac event including heart failure death, sudden cardiac death and fatal acute myocardial infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis selected four parameters, including New York Heart Association (NYHA) functional class, age, gender and left ventricular ejection fraction, without HMR (model 1) and five parameters with the addition of HMR (model 2). The net reclassification improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR and its inclusion was most effective in the downward reclassification of low-risk patients. Nomograms for predicting 5-year cardiac mortality were created from the five-parameter regression model. CONCLUSION: Cardiac MIBG imaging had a significant additive value for predicting cardiac mortality. The prediction formula and nomograms can be used for risk stratifying in patients with CHF.

Effects of oral nicorandil therapy on sympathetic nerve activity and cardiac events in patients with chronic heart failure: subanalysis of our previous report using propensity score matching.

PURPOSE: Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in patients with ischaemic heart disease. However, the long-term effects on both CSNA, as evaluated by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, and prognosis have not been determined in patients with chronic heart failure (CHF). METHODS: This study was a subanalysis of our previous results that serial (123)I-MIBG scintigraphic studies are the most useful prognostic indicator in CHF patients. The study group comprised 208 patients with CHF (left ventricular ejection fraction <45 %) but no cardiac events for at least 5 months identified on the basis of a history of decompensated acute heart failure requiring hospitalization. These patients underwent (123)I-MIBG scintigraphy and echocardiography just before leaving the hospital and again 6 months later. We selected 170 patients and used propensity propensity score matching to compare patients who received oral nicorandil (85 patients) and those who did not (85 patients). The patients were followed up for a median of 5.03 years, with the primary and secondary study end-points defined as the occurrence of a fatal cardiac event and a major adverse cardiac event (MACE), respectively. RESULTS: After treatment, the extent of changes in (123)I-MIBG scintigraphic and echocardiographic parameters in the nicorandil group were more favourable than in those not receiving nicorandil. Of the 170 patients, a fatal cardiac event occurred in 42, and a MACE in 68 during the study. Multivariate Cox regression analyses revealed that no nicorandil treatment was a significant predictor of both cardiac death and MACE in our patients with CHF. On Kaplan-Meier analysis, the rates of freedom from cardiac death or from MACE in the nicorandil group were significantly higher than in those not receiving nicorandil (all p<0.05). CONCLUSION: Long-term nicorandil treatment improves CSNA and left ventricular parameters in patients with CHF. Furthermore, this agent is potentially effective for reducing the incidence of cardiac events in patients with CHF.

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.

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.

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.

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.

Relationship between late ventricular potentials and myocardial 123I-metaiodobenzylguanidine scintigraphy in patients with dilated cardiomyopathy with mild to moderate heart failure: results of a prospective study of sudden death events.

PURPOSE: Late ventricular potentials (LPs) are considered to be useful for identifying patients with heart failure at risk of developing ventricular arrhythmias. (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, which is used to evaluate cardiac sympathetic activity, has demonstrated cardiac sympathetic denervation in patients with malignant ventricular tachyarrhythmias. This study was undertaken to clarify the relationship between LPs and (123)I-MIBG scintigraphy findings in patients with dilated cardiomyopathy (DCM). METHODS: A total of 56 patients with DCM were divided into an LP-positive group (n = 24) and an LP-negative group (n = 32). During the compensated period, the delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-MIBG images and plasma brain natriuretic peptide (BNP) concentrations were measured. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were simultaneously determined by echocardiography. RESULTS: LVEDV, LVESV, LVEF and plasma BNP concentrations were similar in the two groups. However, TDS was significantly higher (35 ± 8 vs. 28 ± 6, p < 0.005), the H/M ratio was significantly lower (1.57 ± 0.23 vs. 1.78 ± 0.20, p < 0.005), and the WR was significantly higher (60 ± 14% vs. 46 ± 12%, p < 0.001) in the LP-positive than in the LP-negative group. The average follow-up time was 4.5 years, and there were nine sudden deaths among the 56 patients (16.1%). In logistic regression analysis, the incidences of sudden death events were similar in those LP-negative with WR <50%, LP-negative with WR ≥ 50% and LP-positive with WR <50% (0%, 10.0% and 14.3%, respectively), but was significantly higher (41.2%) in those LP-positive with WR ≥ 50% (p < 0.01, p < 0.05, and p < 0.05, respectively). CONCLUSION: The present study demonstrated that the values of cardiac (123)I-MIBG scintigraphic parameters were worse in LP-positive DCM patients than in LP-negative DCM patients. Furthermore, in LP-positive DCM patients with a high WR, the incidence of sudden death events was higher than that in other subgroups of DCM patients.

Olmesartan improves coronary flow reserve of hypertensive patients using coronary magnetic resonance imaging compared with amlodipine.

OBJECTIVES: Hypertension impairs coronary endothelial cell function, coronary microvascular function and the coronary flow (CF) reserve (CFR). Angiotensin II receptor blockers (ARBs) have been reported to possibly improve coronary endothelial function and coronary microvascular function. The purpose of this study was to determine whether treatment with the ARB olmesartan was more effective for improving CFR than the calcium channel blocker amlodipine. METHODS: Twenty patients with untreated essential hypertension (M/F = 13/7, aged 55.6 ± 11.6 years) were randomly assigned to treatment with either olmesartan (n = 10) or amlodipine (n = 10) for 6 months. CF was measured in the proximal left anterior descending artery by magnetic resonance imaging before and during intravenous infusion of adenosine. CFR was calculated as the ratio of the hyperemic to baseline diastolic peak flow before and after 6 months of treatment. RESULTS: The extent of systolic blood pressure reduction was similar in both groups (-40.0 ± 19.1 vs. -48.8 ± 14.7 mm Hg, p = 0.26). The olmesartan group showed significant improvement of CFR (from 1.9 ± 1.0 to 3.1 ± 1.1, p = 0.005), but this did not occur in the amlodipine group. CONCLUSION: Olmesartan, but not amlodipine, improves CFR in hypertensive patients.

Relation between connective tissue growth factor and cardiac sympathetic nerve activity in heart failure in DCM patients.

Cardiac fibrosis is an important process of myocardial remodeling. Connective tissue growth factor (CTGF) is a cytokine that plays a key role in the occurrence of progressive fibrosis and excessive scarring. CTGF levels are increased in the failing heart. In addition, sympathetic nerve activity is enhanced in the failing heart, and exacerbates heart failure. To clarify the relation between cardiac sympathetic nerve activity and CTGF, we studied 35 (M/F = 28/7 patients) aged 57 ± 15 years with dilated cardiomyopathy (DCM). Cardiac sympathetic nerve activity was estimated from the total defect score (TDS) and from the H/M ratio and washout rate (WR) on I-123-MIBG imaging. Cardiac symptoms (NYHA class), exercise capacity (specific activity scale: SAS), brain natriuretic peptide (BNP), hemodynamics, and CTGF were assessed. There was a significant correlation between the CTGF and WR on I-123-MIBG (r = 0.45, P = 0.008). Also, a higher plasma CTGF level was associated with a lower SAS score (r = 0.51, P = 0.002), but not the TDS, H/M ratio, or BNP concentration. Moreover, a higher NYHA class and pulmonary artery wedge pressure were associated with a higher plasma CTGF level. The plasma CTGF level can be strongly related with cardiac sympathetic nerve activity in heart failure in DCM patients.