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Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Aims Royal jelly, a creamy substance secreted by honeybees, has been reported to have beneficial effects against dyslipidemia and metabolic syndrome. However, the effects of royal jelly on atherogenesis remain unknown. Hence, we prospectively evaluated whether royal jelly augments vascular endothelial function, which can reflect early atherogenesis, in healthy volunteers. Methods This was a single-center, double-blind, 1:1 randomized placebo-controlled study conducted from October 2018 to December 2019. A total of 100 healthy volunteers were randomly assigned to receive either royal jelly 690 mg or placebo daily for 4 weeks. The primary endpoint was augmentation in vascular endothelial function as assessed using the change in the reactive hyperemia peripheral arterial tonometry index (RH-PAT) index, and the secondary endpoints were the changes in liver function and lipid profiles between baseline and 4 weeks after enrollment. Results The mean age of the participants was 35.0±9.3 years in the placebo group and 36.1±9.1 years in the royal jelly groups; 45% and 50% of the placebo and the royal jelly groups, respectively, were male. The percentage relative change in the RH-PAT index was significantly higher in the royal jelly group than in the placebo group (21.4%±53.1% vs. 0.05%±40.9%, P=0.037). The percentage relative changes in alanine aminotransferase and γ-glutamyl transpeptidase were significantly lower in the royal jelly group than in the placebo group (alanine aminotransferase: -6.06%±22.2% vs. 11.6%±46.5%, P=0.02; γ-glutamyl transpeptidase: -3.45%±17.8% vs. 4.62%±19.4%, P=0.045). Lipid profiles were not significantly different between the two groups. Conclusions Royal jelly might have antiatherogenic property by improving vascular endothelial function. It also augmented liver functions in healthy volunteers.

A 41-year-old Japanese man was admitted to our hospital with acute perimyocarditis 4 weeks after coronavirus disease 2019 (COVID-19) infection. Ten days after admission, the patient showed bilateral facial nerve palsy in the course of improvement of perimyocarditis under treatment with aspirin and colchicine. After prednisolone therapy, perimyocarditis completely improved, and the facial nerve palsy gradually improved. Acute perimyocarditis and facial nerve palsy can occur even 4 weeks after contracting COVID-19., Internal Medicine, 61 (15), pp. 2327-2332; 2022

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC.CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

A 17-year-old boy with acute coronary syndrome was admitted to our hospital. He had xanthomas over his elbow and Achilles tendon and a high level of low-density lipoprotein cholesterol; therefore, his initial diagnosis was familial hypercholesterolemia. However, a genetic analysis revealed a compound heterozygous mutation in the ABCG5 gene with a high serum level of sitosterol, leading to the diagnosis of sitosterolemia. After lipid-lowering treatment, percutaneous coronary intervention was performed. Furthermore, a persistently high C-reactive protein level and images of large arteries led to a diagnosis of Takayasu arteritis. To our knowledge, this is the first case of sitosterolemia complicated by Takayasu arteritis.

Background The cardio-ankle vascular index (CAVI) is an indicator of arterial stiffness and has been reported to be associated with the severity of coronary artery disease and cardiovascular events. However, whether CAVI can predict the composition of coronary plaques remains unclear. Methods We enrolled 208 patients who underwent percutaneous coronary intervention (PCI) for culprit lesions evaluated with iMAP-intravascular ultrasound (IVUS), a radiofrequency imaging system for characterizing tissues. iMAP-IVUS classified the culprit plaque composition as fibrotic, lipidic, necrotic, or calcified, and the respective absolute volumes [fibrotic volume (FV), lipidic volume (LV), necrotic volume NV, and calcified volume] and their ratios (%) within the total plaque volume were calculated. A plaque with a median %NV of ≥ 33.2% was defined as a larger NV (LNV) plaque. We measured CAVI and divided the patients into two groups according to CAVI ≥8 (high CAVI, n = 164) or Results Culprit plaques had significantly greater absolute NV (p = 0.016), %NV (p = 0.01), and smaller %FV (p = 0.02) in patients with high CAVI than in those with low CAVI. Patients with high CAVI had a higher prevalence of LNV plaques in culprit lesions than those with low CAVI (54% vs. 34%, p = 0.026). CAVI correlated significantly and positively with absolute NV, LV, and negatively with %FV. In logistic regression analysis after adjustment for the classic coronary risk factors and possible variables associated with vulnerable plaques, high CAVI had an independent and significant association with the presence of LNV plaques (OR, 3.37; 95% CI, 1.45–7.79; p = 0.0032). Conclusions A high CAVI is associated with the composition of coronary culprit plaques, particularly increased amount of necrotic tissue, in patients with coronary artery disease undergoing PCI .

Autonomic disorders are common in patients with systemic lupus erythematosus (SLE), but the therapeutic strategy and methods for evaluating the effects of therapy have not been established. We describe the three cases of SLE patients who developed severe autonomic disorders as demonstrated by the head-up tilt table test (HUT). All three patients were treated by intensive immunosuppressive treatments including intravenous cyclophosphamide (IVCY); their HUT results all became negative. Our cases suggest that IVCY treatment can be a good therapeutic option for severe autonomic disorders in SLE patients. The HUT is a useful objective method for the diagnosis of and the evaluation of longitudinal therapeutic effects on autonomic disorders in SLE patients with orthostatic intolerance., Modern Rheumatology Case Reports, 6 (1), pp. 47-51; 2022

Objective To determine whether autonomic dysfunction in neurosarcoidosis is associated with anti-ganglionic acetylcholine receptor (gAChR) antibodies, which are detected in autoimmune autonomic ganglionopathy. Methods We retrospectively extracted cases of sarcoidosis from 1787 serum samples of 1,381 patients between 2012 and 2018. Anti-gAChR antibodies against the α3 and β4 subunit were measured by luciferase immunoprecipitation to confirm the clinical features of each case. We summarized literature reviews of neurosarcoidosis with severe dysautonomia to identify relevant clinical features and outcomes. Results We extracted three new cases of neurosarcoidosis with severe dysautonomia, among which two were positive for anti-gAChR antibodies: Case 1 was positive for antibodies against the β4 subunit, and Case 2 was positive for antibodies against both the α3 and β4 subunits. We reviewed the cases of 15 patients with neurosarcoidosis and severe dysautonomia, including the three cases presented herein. Orthostatic hypotension and orthostatic intolerance were the most common symptoms. Among the various types of neuropathy, small fiber neuropathy (SFN) was the most prevalent, with seven of nine cases exhibiting definite SFN. Six of eight cases had impaired postganglionic fibers, of which the present three cases revealed abnormality of 123I-MIBG myocardial scintigraphy. Of the 11 cases, 10 were responsive to immunotherapy, except one seropositive case (Case 2). Conclusions The presence of gAChR antibodies may constitute one of the mechanisms by which dysautonomia arises in neurosarcoidosis.

BACKGROUND Collagen disease is an important cause of aortic regurgitation (AR). Although aortic valve surgery is recommended for patients with AR and depressed left ventricular (LV) function, there have been few reports about risk factors for LV dysfunction in patients with AR concomitant with collagen disease. METHODS AND RESULTS We conducted this study at Kumamoto University Hospital in Japan. A total of 41 patients who had moderate to severe AR and concomitant collagen disease between January 2014 and December 2019 were enrolled. With regard to baseline characteristics, there were no significant differences in the type of collagen disease or El Khoury class between patients with preserved LV function and those with reduced LV function. B-type natriuretic peptide (375.2 [257.9-3852.6]pg/ml vs. 64.0 [33.3-133.6]pg/ml, p

A 62-year-old woman with activity-dependent two-to-one atrioventricular block (2:1AVB) and a normal left ventricular ejection fraction was referred to our department for the evaluation of exclusively exercise-induced marked symptoms. The treadmill test helped establish a clear correlation between 2:1AVB and symptoms. The test results demonstrated that exercise-induced marked symptoms were attributed to abrupt transient hypotension combined with relative bradycardia, probably due to increased diastolic mitral and tricuspid regurgitation because of 2:1AVB during moderate-to-heavy exercise. After pacemaker implantation for 2:1AVB, the symptoms and transient hypotension disappeared, and her exercise capacity improved.

Objective Associations between aortic stiffness and cardiovascular disease events are mediated in part by pathways that include coronary microvascular dysfunction (CMD) and remodeling. However, the relationship between aortic stiffness and CMD remains unclear. The present study aimed to determine whether aortic stiffness causes CMD as evaluated by the hyperemic microvascular resistance index (hMVRI) in patients with non-obstructive coronary artery disease (CAD). Methods The intracoronary physiological variables in 209 coronary arteries were evaluated in 121 patients with non-obstructive CAD (fractional flow reserve >0.80) or reference vessels. The cardio-ankle vascular index (CAVI) as a measure of aortic stiffness and atherosclerotic risk factors were also measured. Results Univariate analyses showed that hMVRI correlated with age (β=0.24, p=0.007), eicosapentaenoic acid (EPA; β=-0.18, p=0.048), EPA/arachidonic acid (AA) (EPA/AA) ratio (β=-0.22, p=0.014) and CAVI (β=0.30, p=0.001). A multivariate regression analysis identified CAVI (β=0.25, p=0.007) and EPA/AA ratio (β=-0.26, SE=0.211, p=0.003) as independent determinants of hMVRI. Conclusion Aortic stiffness may cause CMD in patients with non-obstructive CAD via increased coronary microvascular resistance. Aortic stiffness is associated with CMD which is evaluated as hyperemic microvascular resistance in patients with non-obstructive CAD.

The number of patients aged over 90 years undergoing transthoracic echocardiography (TTE) has increased. Normal echocardiographic measurement values in healthy Japanese aged 20-79 years have been reported by Daimon et al., and in those aged 10-89 years by Okura et al. To date, no researchers have published normal values in healthy Japanese aged over 90 years. To understand the echocardiographic characteristics and establish the normal range, we evaluated patients aged over 90 years who had preserved left ventricular (LV) ejection fraction without cardiovascular disease.Enrolled in the study were consecutive patients aged over 90 years who were examined by TTE at the Ultrasound Imaging Center at Nagasaki University Hospital, Japan, between September 2009 and May 2016. We selected patients with LV ejection fraction 55%, and without cardiac, renal, or aortic disease.Among a total of 956 patients, 73 patients (19 males, 54 females) were admitted. Compared with females, males had significantly higher values of aortic diameter at the sinus of Valsalva and LV diastolic diameter and systolic diameter (P 0.01), significantly lower E wave velocities (P 0.01) and left ventricle mass (P 0.01), and lower values of relative wall thickness (P 0.01). Compared with subjects in their 70s and 80s in the studies by Daimon and Okura, the E and A wave velocities were higher.We established the normal range of TTE parameters in elderly patients who had LV ejection fraction55% without cardiac, renal, or aortic disease. Sex differences were present as well as a tendency towards age-related changes in LV geometry and diastolic function. Most of the patients aged over 90 years had LV hypertrophy and potential diastolic dysfunction.

A 73-year-old Japanese man was admitted with an asymptomatic pulmonary artery aneurysm. However, chest X-ray and contrast-enhanced thoracic computed tomography revealed a protrusion at the second left branch that in fact was a pulmonary artery aneurysm with a diameter of 50 mm. Transesophageal echocardiography showed a bicuspid pulmonary valve, and cardiac catheterization revealed pulmonary stenosis with a pressure gradient of 45 mmHg, but no other heart diseases were noted. An extremely rare pulmonary artery aneurysm associated with an isolated bicuspid pulmonary valve was diagnosed.

A 54-year-old Japanese woman was admitted to our ward because of recurrent chest pain at rest for 2 months. She had been treated with nivolumab, an immune checkpoint inhibitor for inoperable advanced hypopharyngeal cancer for 21 months. She had no chest pain after cessation of nivolumab treatment. Cardiac catheterization confirmed the presence of vasospastic angina. Benidipine 8 mg was started, and she had no chest pain even after resuming therapy with nivolumab. Vasospastic angina is an adverse effect of nivolumab.

This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed. During a median follow-up of 615 days, 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.1 ± 7.4 years vs. 78.2 ± 6.2 years, p = 0.009) and had significantly higher interventricular septal thickness in diastole (16.6 ± 3.1 mm vs. 15.3 ± 2.4 mm, p = 0.048), lower RV-GLS (10.9 ± 2.7% vs. 12.8 ± 3.5%, p = 0.010), and lower right ventricular free wall longitudinal strain (RVFWLS) (13.1 ± 3.3% vs. 15.5 ± 3.8%, p = 0.004). In the univariate Cox proportional hazard analysis, age, left atrial volume index (LAVI), RV-GLS, and RVFWLS were significantly associated with cardiovascular death [age, hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.02-1.19, p = 0.010; LAVI, HR, 1.02; 95% CI, 1.00-1.03, p = 0.009; RV-GLS, HR, 0.86; 95% CI, 0.75-0.97, p = 0.017; RVFWLS, HR 0.89; 95% CI, 0.79-1.00; p = 0.041]. Multivariable Cox proportional hazard analysis showed RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (HR, 0.86; 95% CI, 0.74-0.99; p = 0.038). Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cut-off value of RV-GLS was 11.59% (sensitivity, 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (11.59%) had a significantly higher probability of total cardiovascular death (p = 0.004) and heart failure-related hospitalization (p = 0.013).RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic findings.

Background The impact of intra-atrial conduction delay on the recurrence of atrial tachyarrhythmia after radio frequency catheter ablation (RFCA) has not been fully elucidated. Methods We retrospectively analyzed 155 AF patients who were sinus rhythm at the start of RFCA. The conduction time from the onset of the earliest atrial electrogram at the high right atrium (HRA) to the end of the latest electrogram at the coronary sinus (CS) during sinus rhythm was defined as HRA-CS conduction time. Pulmonary vein isolation (PVI) was performed followed by linear roof lesion and complex fractionated atrial electrogram (CFAE) ablation until AF termination. We evaluated atrial tachyarrhythmia recurrence 12 months after RFCA. Results The follow-up data were available for 148 patients. The recurrence of atrial tachyarrhythmia was noted in 28 (18.9%) patients. Atrial tachyarrhythmia recurrence patients had longer HRA-CS conduction times (151.3 ± 22.1 ms vs 160.1 ± 32.6 ms, p = .017). The patients were divided into the long or short HRA-CS conduction time group. The Kaplan–Meier analysis revealed that the long HRA-CS conduction time group held a higher risk of atrial tachyarrhythmia recurrence (log-rank test, p = .019). The multivariable Cox hazard analysis revealed that a long HRA-CS conduction time was a significant risk factor for the recurrence of atrial tachyarrhythmia, despite a long AF duration, persistent AF, and larger left atrial diameter (LAD) were not statistically significant. Conclusions The HRA-CS conduction time was the primary influencing factor that predicted the recurrence of atrial tachyarrhythmia after catheter ablation.

AIMS The prediction of future heart failure (HF) in stable outpatients is often difficult for general practitioners and cardiologists. Recently, the H2 FPEF score (0-9 points) has been proposed for the discrimination of HF with preserved ejection fraction from non-cardiac causes of dyspnoea. The six clinical and echocardiographic variables that constitute the H2 FPEF score include the following: (i) obesity (H); (ii) the use of ≥2 antihypertensive drugs (H); (iii) atrial fibrillation (F); (iv) pulmonary hypertension (P); (v) an age > 60 years (E); and (vi) E/e' > 9 (F). We performed an external validation study that investigated whether the H2 FPEF score could predict future HF-related events in stable outpatients with cardiovascular risk factor(s) in Japan. METHODS AND RESULTS In this prospective cohort study, after exclusion of 195 from 551 consecutive, stable Japanese outpatients with at least one cardiovascular risk factor who were enrolled between September 2010 and July 2013, the remaining 356 outpatients (171 men, 185 women, mean age 73.2 years) were eligible for the analysis. We calculated the H2 FPEF score (0-9 points), and followed up the patients for an average of 517 days. In all of the 356 patients, the mean H2 FPEF score was 3.1 ± 1.8, and 15 developed HF-related events during the follow-up period, including cardiovascular death (n = 2) and hospitalization for HF decompensation (n = 13). Multivariate Cox proportional hazards analysis showed that the H2 FPEF score was an independent predictor of future HF-related events (P < 0.001 for all three models). Kaplan-Meier survival curves showed a significantly higher probability of HF-related events in the outpatients with a high H2 FPEF score (P < 0.001). In receiver operating characteristic (ROC) curve analysis, the H2 FPEF score was significantly associated with the occurrence of future HF-related events (P < 0.001). In ROC curve analysis, the sensitivity, specificity, and positive likelihood ratio of a H2 FPEF score of 7 points to predict HF-related events were 47%, 96%, and 11.4%, respectively. CONCLUSIONS The H2 FPEF score could provide useful information for future HF-related events in stable outpatients with cardiovascular risk factor(s) in Japan.

Objective Polyunsaturated fatty acids (PUFAs) are associated with heart failure (HF) as well as coronary artery disease. However, little is known about the relationships between PUFAs and the exercise responses of patients with HF. We evaluated the relationships between PUFAs and the parameters of cardiopulmonary exercise tests (CPETs) in patients with non-ischemic HF. Methods Fifty patients with stable non-ischemic HF underwent CPETs at our hospital. Data were analyzed to evaluate the relationships between PUFAs and echocardiographic findings as well as CPET and other test parameters. Results Correlations were significant and negative between dihomo-γ-linolenic acid (DGLA) + arachidonic acid (AA) and minute ventilation versus carbon dioxide production (VE/VCO2) slope, and positive between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and VE/VCO2 slope. A multivariate regression analysis selected DGLA+AA and AA as independent predictors of VE/VCO2 slope. However, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) were not significantly correlated with the CPET parameters. Conclusion Low levels of circulating DGLA+AA and AA among PUFAs were associated with decreased exercise responses in patients with stable non-ischemic HF. These findings suggest that high levels of omega-6 PUFAs may improve the clinical outcomes of patients with non-ischemic HF via their effects on exercise responses., Internal Medicine, 58(22), pp.3219-3225; 2019

The target of diastolic blood pressure (DBP) remains controversial in patients with coronary artery disease (CAD). We systematically searched PubMed/Medline and the Cochrane Central database for randomized controlled trials (RCTs) assessing the efficacy and safety of reducing DBP in CAD patients from January 1965 to July 2017. Seven placebo-controlled RCTs enrolling 34,814 CAD patients who achieved DBP

Aims This study was performed to investigate whether left atrial (LA) strain by echocardiography provides prognostic information in patients with wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM). Methods and results Among 129 patients who were diagnosed with ATTRwt‐CM at Kumamoto University Hospital from December 2002 to December 2019, 113 patients who had enough information for two‐dimensional speckle tracking echocardiography were enrolled in this study. During a median follow‐up of 668 days, 28 cardiovascular deaths occurred. Compared with patients in the non‐event group, those in the cardiovascular death group were significantly older (81.5 ± 7.4 vs. 78.1 ± 6.1 years, P

Restrictive cardiomyopathy (RCM) is a rare primary myocardial disease, and its pathological features are yet to be determined. Restrictive cardiomyopathy with MHY7 mutation was diagnosed in a 65-year-old Japanese woman. Electron microscopy of a myocardial biopsy revealed electron-dense materials resulting from focal myocyte degeneration and necrosis as well as tubular structures and pseudo-inclusion bodies in some nuclei. These features may be associated with the pathogenesis of RCM.

A 16-year-old Japanese man was admitted to our hospital because of syncope during exercise. His father and his younger brother had permanent pacemaker implantation because of sick sinus syndrome. Several examinations revealed first-degree atrioventricular block, complete right bundle branch block, sick sinus syndrome, and ventricular tachycardia with normal cardiac function. As no abnormalities were evident on coronary angiography, right ventricular endomyocardial biopsy was performed. It showed myocardial disarrangement and lipofuscin accumulation in hypertrophic myocytes. Moreover, electron microscopy showed a few degenerative myocytes, Z-band streaming, disarrangement, increased small capillaries with Weibel-Palade bodies in endothelial cells, and endothelial proliferations. Genetic analysis of the proband, his father, and his younger brother revealed a missense mutation, D1275N, in SCN5A, a gene which encodes sodium ion channel protein, are related to cardiomyopathy and arrhythmia. The proband was diagnosed with a cardiac conduction defect (CCD) and underwent permanent pacemaker implantation. These pathological findings suggest various myocardial changes presented in CCD patients with a missense mutation, D1275N, in SCN5A.

Objective This study was performed to investigate the physical performance parameters, including lower extremity function parameters, that may be risk factors for falls in patients with chronic heart failure. Methods Seventy patients with stable chronic heart failure were included in this retrospective cross-sectional study. The five-repetition sit-to-stand test (5STS) time, Controlling Nutritional Status (CONUT) score, and number of drugs were assessed. Results Simple linear regression analysis revealed that the 5STS time was positively correlated with age, the CONUT score, and the number of drugs but was negatively associated with the handgrip force, quadriceps force, and quadriceps muscle thickness. Multiple linear regression analysis showed a significant association between the 5STS time and the CONUT score, quadriceps force, and number of drugs. Conclusion The muscle strength, nutritional status, and number of drugs should be evaluated to prevent lower extremity weakness in patients with stable chronic heart failure.

This study examined whether using an artificial neural network (ANN) helps beginners in diagnostic cardiac imaging to achieve similar results to experts when interpreting stress myocardial perfusion imaging (MPI). One hundred and thirty-eight patients underwent stress MPI with Tc-labeled agents. An expert and a beginner interpreted stress/rest MPI with or without the ANN and the results were compared. The myocardium was divided into 5 regions (the apex; septum; anterior; lateral, and inferior regions), and the defect score of myocardial blood flow was evaluated from 0 to 4, and SSS, SRS, and SDS were calculated. The ANN effect, defined as the difference in each of these scores between with and without the ANN, was calculated to investigate the influence of ANN on the interpreters' performance. We classified 2 groups (insignificant perfusion group and significant perfusion group) and compared them. In the same way, classified 2 groups (insignificant ischemia group and significant ischemia group) and compared them. Besides, we classified 2 groups (normal vessels group and multi-vessels group) and compared them. The ANN effect was smaller for the expert than for the beginner. Besides, the ANN effect for insignificant perfusion group, insignificant ischemia group and multi-vessels group were smaller for the expert than for the beginner. On the other hand, the ANN effect for significant perfusion group, significant ischemia group and normal vessels group were no significant. When interpreting MPI, beginners may achieve similar results to experts by using an ANN. Thus, interpreting MPI with ANN may be useful for beginners. Furthermore, when beginners interpret insignificant perfusion group, insignificant ischemia group and multi-vessel group, beginners may achieve similar results to experts by using an ANN.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.

Although the Klotho gene is recognized as an aging-suppressor gene, the clinical significance of its soluble product, soluble Klotho, in coronary artery disease (CAD) has not been completely determined. The relationship between soluble Klotho and coronary artery calcification (CAC) was investigated in patients with stable CAD.CAC in culprit lesions was analyzed in 75 non-dialysis patients with stable CAD who were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). The main outcome measure was the calcium index (CalcIndex), a volumetric IVUS-derived measure of total calcification per culprit lesion. A low CalcIndex was defined as a first-quartile calcium index (0.042). Patients were divided into two groups according to the median serum Klotho value: low Klotho (n = 37, ≤460 pg/mL) and high Klotho (n = 38,460 pg/mL).The CalcIndex was significantly lower in patients with high than with low Klotho. Patients with high Klotho had a significantly higher prevalence of a low CalcIndex than those with low Klotho. The number of angiographic moderate-severe CACs in whole coronary arteries was significantly decreased in patients with high Klotho compared to low Klotho. Serum Klotho levels correlated significantly and inversely with the CalcIndex. This relationship was pronounced in patients with estimated glomerular filtration rate60 mL/min/1.73 mHigh serum soluble Klotho levels are associated with a low degree of CAC in non-dialysis, stable CAD patients treated by PCI.

Objectives To compare the effects of nicorandil and nitroglycerin on arterial oxygenation during two-lung ventilation (TLV) and one-lung ventilation (OLV) in patients with risk factors for myocardial ischemia. Design A prospective, randomized, double-blind study. Setting A tertiary care hospital. Participants Fifty-six patients scheduled for elective video-assisted thoracic surgery were assigned randomly to either the nicorandil group or the nitroglycerin group. Interventions Patients in the nicorandil group received a bolus dose of nicorandil, 0.08 mg/kg during induction of anesthesia, followed by a continuous infusion at a rate of 0.08 mg/kg/h. Patients in the nitroglycerin group received a continuous infusion of nitroglycerin at a rate of 1 µg/kg/min from the induction of anesthesia. Measurements and Main Results Arterial blood gas analysis was performed at the following points: before induction of anesthesia; during TLV; at 5, 10, 20, and 30 minutes after the initiation of OLV. PaO2 at TLV (479.7 ± 57.1 v 408.2 ± 70.9 mmHg, p Conclusion This study demonstrated that oxygenation during TLV and OLV was significantly higher in patients receiving nicorandil than in those receiving nitroglycerin.

A 45-year-old Japanese man was referred to our hospital with chest and back pain with a duration of two days. Contrast-enhanced computed tomography (CT) showed a large calcified lesion in the inferior vena cava (IVC),thrombus with calcification in the pulmonary arteries of the left lower lobe, and an infiltrative shadow in the left lower lobe. He was diagnosed with pulmonary thromboembolism (PE) and pneumonia. Calcification in the IVC was not evident on any CT images obtained six and eight years earlier. This patient was identified to be an extremely rare case of PE associated with IVC calcification that developed during adulthood., Internal medicine, 58(13), pp.1907-1912; 2019

The consumption of omega-3 polyunsaturated fatty acids (PUFAs) reduces the incidence of cardiovascular events and sudden cardiac death. Coronary microvascular dysfunction (CMD) is a predictor of cardiac mortality, but little information is known on the relationship between CMD and omega-3 PUFAs. This study aimed to identify the relationship between the serum levels of omega-3 PUFAs and the CMD evaluated by the hyperemic microvascular resistance index (hMVRI) to assess coronary microvascular function in patients with stable coronary artery disease (CAD). Intracoronary physiological variables (fractional flow reserve (FFR),hMVRI, mean distal coronary pressure (Pd), and average peak velocity (APV)) were measured in 108 patients. These parameters were evaluated in 150 coronary arteries with stenosis of intermediate severity and without significant ischemia (FFR > 0.80). The PUFA levels and atherosclerotic risk factors were also measured. Univariate analysis shows that hMVRI was negatively correlated with eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (β = ?0.31, P = 0.001) and EPA (β = ?0.25, P = 0.009) and was positively correlated with dihomo-γ-linolenic acid (β = 0.26, P = 0.006). Multivariate regression analysis shows that the EPA/AA ratio was the only independent determinant of hMVRI (β = ?0.234, SE = 0.231, P = 0.024). Furthermore, hMVRI decreased significantly from the lowest to highest tertiles of the EPA/AA ratio (P = 0.007). The EPA/AA ratio was positively correlated with APV at hyperemia (β = 0.26, P = 0.008) but not with Pd at hyperemia. A lower serum EPA/AA ratio may cause CMD in patients with stable CAD., International Heart Journal, 59(6), pp.1194-1201; 2018

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients’ demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients’ demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p

Electrocardiography (ECG) is used to screen for pulmonary hypertension (PH). However, it is unclear which parameters of ECG are the most useful for screening.ECG parameters related to right ventricular hypertrophy criteria were examined in 145 ECGs of subjects who were suspected to have PH and underwent right heart catheterization (RHC) (age 58.4 ± 17.5 years, 112 women, mean pulmonary arterial pressure [MPAP] 35.4 ± 13.3 mmHg). Based on the results of RHC, 108 subjects had PH (56 pulmonary arterial hypertension [PAH] and 52 chronic thromboembolic pulmonary hypertension [CTEPH]).Fourteen of 17 ECG parameters in the present study were significantly associated with PH on univariate analysis. On multivariable logistic regression analysis, S wave depth in lead V5 (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.10-1.47) and depth of T wave inversion in lead V4 (OR 1.21, 95% CI 1.03-1.46) were independent predictors of MPAP ≥ 25 mmHg, and the cut-off values determined by receiver operating characteristic curve analyses were 0.42 mV and -0.28 mV, respectively.In conclusion, a deeper S wave in lead V5 and the presence of a wider extent of negative T waves in the precordial leads may be clinically simple and useful ECG parameters for screening for PH.

Calcified amorphous tumor (CAT) is a rare, non-neoplastic tumor involving calcium deposition in amorphous materials. Although its etiology is unknown, cases have frequently been reported in patients with hemodialysis for chronic kidney disease. We herein describe a case of cardiac CAT in a 64-year-old woman who had been on hemodialysis for diabetic nephropathy for 20 years, and the findings of the present patient, in association with the findings of previous case reports, suggest that end-stage renal disease seems to play an important role in the onset of CAT, especially in CAT formation at the mitral annulus, which appears to differ from CAT occurring at other sites., Internal Medicine, 56(22), pp.3057-3060; 2017

Background Nonthermal atmospheric pressure plasma (NTAPP) has recently received attention as a novel tool in medicine. It is thought that plasma components yield plasma effects such as sterilization, blood coagulation, and wound healing. These effects are produced without thermal damage. We investigated the blood coagulation effect of NTAPP by using a multigas plasma jet. Materials and methods Multigas plasma jets can generate NTAPP by several gas species. In this study, argon, oxygen, helium, nitrogen, mock air, and carbon dioxide were used to generate NTAPP, and blood coagulation times were compared with each plasma-treated sample. The NTAPP blood coagulation effects on whole blood with four different anticoagulants were investigated. In addition, in this study, the effects of plasma treatment on porcine tissues and organs were investigated as in vivo experiment. Results A tendency to coagulate later with argon gas plasma than others was shown. There were no significant differences between oxygen, helium, nitrogen, mock air, and carbon dioxide. Whole blood with each anticoagulant demonstrated fast coagulation by NTAPP treatment. Fast control of the bleeding lesions on porcine stomach and liver by plasma treatment was observed, and no tissue damage due to the plasma treatment was detected by optical microscope. Conclusions These experiments suggest the potential of various gas NTAPPs as a novel medical device to control bleeding lesions.

A 58-year-old Japanese woman with herpes zoster developed Behcet's disease (BD) with symptoms including orthostatic intolerance as an autonomic disorder. Multiple immune-suppressive therapies and a β-blocker successfully controlled both the disease activity of BD and the autonomic disorders. A cytokine multiplex analysis of her serum revealed the elevation of proinflammatory cytokines [interleukin (IL)-1, IL-6, IL-12, tumor necrosis factor alfa (TNFα), and interferon gamma (IFN-γ)] and a low IL-10 concentration. IL-10 production is reported to be important for defense against herpes zoster virus (VZV). Insufficient IL-10 production is reported in BD. The reactivation of VZV with this cytokine profile suggests that BD will develop with various symptoms, including severe autonomic disorders., Internal Medicine, 59(8), pp.1099-1104; 2020

Aim Comparisons between the resting full-cycle ratio (RFR), a new physiological resting index, and fractional flow reserve (FFR) in terms of prognostic value are limited. We aimed to identify the prognostic value of concordance between RFR and FFR and to determine the stability of measured RFR. Methods and results We measured FFR and RFR in 161 coronary arteries of 119 patients and classified the data using known cutoffs for FFR (≤0.80) and RFR (≤0.89) into groups; high FFR and high RFR (high FFR/low RFR) group, high FFR and low RFR (high FFR/low RFR) group, low FFR and high RFR (low FFR/high RFR) group, and low FFR and low RFR (low FFR/low RFR) group. The concordance rates in these groups were 42.2% (68/161), 4.4% (7/161), 14.3% (23/161), and 39.1% (63/161), respectively. The concordance between FFR and RFR was 81.4%. The prevalence of females was significantly higher, values for hemoglobin values were significantly lower, and average E/E' (an index of left ventricular (LV) diastolic function by echocardiography) was significantly higher in high FFR/low RFR group than in low FFR/high RFR group (p = .008, .050, and .028, respectively). Conclusions The RFR and FFR values consistently agreed. Female, anemia, and LV diastolic dysfunction may be related to the difference of discordance between high FFR/low RFR and low FFR/high RFR.

Supplemental Digital Content is available in the text, Although serum magnesium (Mg) levels are closely associated with the prognosis of heart failure (HF) patients, the clinical significance of sMg levels on the cardiovascular outcomes of HF with preserved ejection fraction (HFpEF) patients is not fully understood. This study was a retrospective, single-center, observational study. We enrolled 452 consecutive HFpEF patients admitted to Kumamoto University Hospital. We defined lower sMg as

Because diastolic late mitral annular velocity (a') obtained by transthoracic-echocardiography (TTE) represents left atrial (LA) function, we investigated the clinical significance of a' in heart failure (HF) with a preserved left ventricular (LV) ejection fraction (HFpEF).We enrolled 448 consecutive HFpEF patients (sinus rhythm: 66.3%, atrial fibrillation [AF] rhythm: 33.7%) and performed TTE under stable conditions after optimal therapy. In patients with sinus rhythm, a' values were measured at septal mitral annuli.A' had weak but significant negative correlations with the natural-logarithm-B-type natriuretic peptide (Ln-BNP), LA diameter, LV mass index and tricuspid regurgitation pressure gradient. Receiver operating characteristic (ROC) curve analysis showed that the best cut-off value of a' and systolic mitral annular velocity (s') for the prediction of HF-related events were 7.45 cm/s and 6.5 cm/s with areas under the curve (AUC) of 0.841 and 0.682, respectively. The AUC of ROC analysis for the logistic regression model of a' plus s' was improved to 0.97. In Kaplan-Meier analysis, HFpEF patients with low-a' (7.45 cm/s) had a significantly higher risk of total cardiovascular and HF-related events (both p .01 by log-rank test) than those with high-a' (≥ 7.45 cm/s) and were prognostically equivalent to those with AF. Multivariate Cox proportional hazard analysis identified low-a' as an independent predictor of both total cardiovascular (hazard ratio [HR]: 0.823, 95% confidence interval [CI]: 0.714-0.949, p = .007) and HF-related events (HR: 0.551, 95% CI: 0.422-0.720, p .001).A' value measurement is a non-invasive and useful method for risk stratification in HFpEF.