Publications by authors named "Kunihiro Nishimura"

275 Publications

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.

Diabetes Res Clin Pract 2021 Sep 2:109037. Epub 2021 Sep 2.

Division of Diabetes and Lipid Metabolism, National Cerebral and Cardiovascular Center, Suita, Japan.

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.
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http://dx.doi.org/10.1016/j.diabres.2021.109037DOI Listing
September 2021

Antiseizure medications for post-stroke epilepsy: A real-world prospective cohort study.

Brain Behav 2021 Sep 22;11(9):e2330. Epub 2021 Aug 22.

Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.

Background And Purpose: The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE.

Methods: This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens.

Results: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001).

Conclusions: Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.
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http://dx.doi.org/10.1002/brb3.2330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442594PMC
September 2021

Association of hospital performance measures with readmissions for patients with heart failure: A report from JROAD-DPC study.

Int J Cardiol 2021 Oct 20;340:48-54. Epub 2021 Aug 20.

National Cerebral and Cardiovascular Center, Suita, Japan.

Background: Measuring quality of care is central to quality improvement. Improving outcomes for heart failure (HF) may relate to hospital care delivery. However, there is limited nationwide data on the relationship between hospital-level HF performance measures and clinical outcomes.

Methods: From the Japanese Registry of All cardiac and vascular Diseases (JROAD-DPC) database, 83,567 HF patients hospitalised in 731 certificated hospitals in 2014 by the Japanese Circulation Society were analysed. Five performance measures were prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist and measurement rate of echocardiography and B-type natriuretic peptide during hospitalisation. Relationships between these measures and 1-year readmission due to HF were analysed. Composite performance score (CPS) obtained from the five performance measures and outcomes were also analysed. We also investigated the relationships between CPS and hospital structural factors.

Results: From the cohort (mean age; 78.2 years, woman 48.4%), HF readmission rate at 1 year was 19.6% (n = 16,368). Readmission rate decreased with higher quartiles of prescription rate in each medication and diagnostic performance rates. The highest CPS group was associated with a 15% risk reduction in HF readmission compared with the lowest CPS group (hazard ratio, 0.85, 95% confidence interval [0.80-0.89], p < 0.001) after covariate adjustment. Several structural factors such as number of cardiology specialists, hospital case volume for HF, and presence of cardiac surgery division were associated with high CPS.

Conclusion: Higher hospital performance measures for HF were inversely associated with HF readmissions.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.019DOI Listing
October 2021

Impact of Physician Volume and Specialty on In-Hospital Mortality of Ischemic and Hemorrhagic Stroke.

Circ J 2021 Aug 13. Epub 2021 Aug 13.

National Cerebral and Cardiovascular Center.

Background: The degree of association between mortality and case volume/physician volume is well known for many surgical procedures and medical conditions. However, the link between physician volume and death rate in patients hospitalized for stroke remains unclear. This study analyzed the correlation between in-hospital stroke mortality and physician volume per hospital, considering board certification status.Methods and Results:For this retrospective registry-based cohort study, data were obtained from the Japanese nationwide registry on patients hospitalized for ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) between 2010 and 2016. The number of stroke care physicians and relevant board-certified physicians was also obtained. Odd ratios (ORs) of 30-day in-hospital mortality were estimated after adjusting for institutional and patient differences using generalized mixed logistic regression. From 295,150 (ischemic stroke), 98,657 (ICH), and 36,174 (SAH) patients, 30-day in-hospital mortality rates were 4.4%, 16.0%, and 26.6%, respectively. There was a correlation between case volume and physician volume. A higher number of stroke care physicians was associated with a reduction in 30-day mortality after adjusting for stroke case volume and comorbidities for all stroke types (all P for trend<0.05).

Conclusions: An increased number of stroke care physicians was associated with reduced in-hospital mortality for all types of stroke. The volume threshold of board-certified physicians depends on the specialty and stroke type.
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http://dx.doi.org/10.1253/circj.CJ-20-1214DOI Listing
August 2021

Glucose Fluctuation and Severe Internal Carotid Artery Siphon Stenosis in Type 2 Diabetes Patients.

Nutrients 2021 Jul 12;13(7). Epub 2021 Jul 12.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita 564-8565, Japan.

The impact of glucose fluctuation on intracranial artery stenosis remains to be elucidated. This study aimed to investigate the association between glucose fluctuation and intracranial artery stenosis. This was a cross-sectional study of type 2 diabetes mellitus (T2DM) patients equipped with the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories) between February 2019 and June 2020. Glucose fluctuation was evaluated according to the standard deviation (SD) of blood glucose, coefficient of variation (%CV), and mean amplitude of glycemic excursions (MAGE). Magnetic resonance angiography was used to evaluate the degree of intracranial artery stenosis. Of the 103 patients, 8 patients developed severe internal carotid artery (ICA) siphon stenosis (≥70%). SD, %CV, and MAGE were significantly higher in the severe stenosis group than in the non-severe stenosis group (<70%), whereas there was no significant intergroup difference in the mean blood glucose and HbA1c. Multivariable logistic regression analysis adjusted for sex showed that SD, %CV, and MAGE were independent factors associated with severe ICA siphon stenosis. In conclusion, glucose fluctuation is significantly associated with severe ICA siphon stenosis in T2DM patients. Thus, glucose fluctuation can be a target of preventive therapies for intracranial artery stenosis and ischemic stroke.
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http://dx.doi.org/10.3390/nu13072379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308661PMC
July 2021

p.R4810K (c.14429G > A) Variant Determines Anatomical Variations of the Circle of Willis in Cerebrovascular Disease.

Front Aging Neurosci 2021 15;13:681743. Epub 2021 Jul 15.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Introduction: Dysregulation of the RING finger protein 213 gene impairs vascular formation in experimental animal models. In addition, vascular abnormalities in the circle of Willis are associated with cerebrovascular disease. Here, we evaluated the relationship between the East Asian founder variant p.R4810K and consequent anatomical variations in the circle of Willis in cerebrovascular disease.

Patients And Methods: The present study is an observational cross-sectional study. It included patients with acute anterior circulation non-cardioembolic stroke admitted to our institution within 7 days of symptom onset or last-known-well from 2011 to 2019, and those who participated in the National Cerebral and Cardiovascular Center Biobank. We compared anatomical variations of the vessels constituting the circle of Willis between p.R4810K (c.14429G > A) variant carriers and non-carriers using magnetic resonance angiography and assessed the association between the variants and the presence of the vessels constituting the circle of Willis. Patients with moyamoya disease were excluded.

Results: Four hundred eighty-one patients [146 women (30%); median age 70 years; median baseline National Institutes of Health Stroke Scale score 5] were analyzed. The p.R4810K variant carriers ( = 25) were more likely to have both posterior communicating arteries (PComAs) than the variant non-carriers ( = 456) (56% vs. 13%, < 0.01). Furthermore, variant carriers were less likely to have an anterior communicating artery (AComA) than non-carriers (68% vs. 84%, = 0.04). In a multivariate logistic regression analysis, the association of p.R4810K variant carriers with the presence of both PComAs and the absence of AComA remained significant.

Conclusion: Our findings suggest that the p.R4810K variant is an important factor in determining anatomical variations in the circle of Willis.
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http://dx.doi.org/10.3389/fnagi.2021.681743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322682PMC
July 2021

Heatstroke predictions by machine learning, weather information, and an all-population registry for 12-hour heatstroke alerts.

Nat Commun 2021 07 28;12(1):4575. Epub 2021 Jul 28.

Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

This study aims to develop and validate prediction models for the number of all heatstroke cases, and heatstrokes of hospital admission and death cases per city per 12 h, using multiple weather information and a population-based database for heatstroke patients in 16 Japanese cities (corresponding to around a 10,000,000 population size). In the testing dataset, mean absolute percentage error of generalized linear models with wet bulb globe temperature as the only predictor and the optimal models, respectively, are 43.0% and 14.8% for spikes in the number of all heatstroke cases, and 37.7% and 10.6% for spikes in the number of heatstrokes of hospital admission and death cases. The optimal models predict the spikes in the number of heatstrokes well by machine learning methods including non-linear multivariable predictors and/or under-sampling and bagging. Here, we develop prediction models whose predictive performances are high enough to be implemented in public health settings.
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http://dx.doi.org/10.1038/s41467-021-24823-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319225PMC
July 2021

Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome.

Eur Heart J 2021 07;42(29):2854-2863

Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita 5648565, Japan.

Aims: The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability.

Methods And Results: Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves.

Conclusion: In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.
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http://dx.doi.org/10.1093/eurheartj/ehab254DOI Listing
July 2021

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).

Tokai J Exp Clin Med 2021 Jul 20;46(2):59-68. Epub 2021 Jul 20.

Diabetes Center, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusamukaihata-cho, Fushimi-ku, Kyoto, Kyoto 612-8555, Japan.

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.
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July 2021

Comparison of the Japan Society of Clinical Chemistry reference method and CDC method for HDL and LDL cholesterol measurements using fresh sera.

Pract Lab Med 2021 May 23;25:e00228. Epub 2021 Apr 23.

Department of Food and Nutritional Sciences, Practice Center for Registered Dietitian, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi, 487-8501, Japan.

Objectives: In 2009, the Japan Society of Clinical Chemistry (JSCC) recommended a reference method for the measurement of serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. This automated method uses cholesterol esterase-cholesterol dehydrogenase to measure cholesterol levels in fractions obtained after ultracentrifugation and dextran sulfate/magnesium chloride precipitation. In the present study, using fresh samples, we compared the LDL-C and HDL-C levels measured using this method with those measured using the traditional Centers for Disease Control and Prevention (CDC)-beta-quantification (BQ) method.

Design: and methods: Using both the JSCC and CDC-BQ methods, LDL-C/HDL-C levels were measured in 47 non-diseased and 126 diseased subjects, whose triglyceride levels were lower than 11.29 ​mmol/L (1000 ​mg/dL).

Results: For LDL-C, the equation of the line representing the correlation between the two methods was y ​= ​0.991x + 0.009 ​mmol/L; r ​= ​0.999; and Sy/x ​= ​0.025 ​mmol/L, where x is the mean LDL-C level measured using the CDC-BQ method. Similarly, for HDL-C, the equation of the line representing the correlation between the two methods was y ​= ​0.988x + 0.041 ​mmol/L, r ​= ​0.999, and Sy/x ​= ​0.019 ​mmol/L, where x is the mean HDL-C level measured using the CDC-BQ method.

Conclusions: The JSCC method agreed with the CDC-BQ method in cases of both non-diseased and diseased subjects, including those with dyslipidemia.
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http://dx.doi.org/10.1016/j.plabm.2021.e00228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145738PMC
May 2021

Impact of Chronic Kidney Disease on In-Hospital and 3-Year Clinical Outcomes in Patients With Acute Myocardial Infarction Treated by Contemporary Percutaneous Coronary Intervention and Optimal Medical Therapy - Insights From the J-MINUET Study.

Circ J 2021 Jun 3. Epub 2021 Jun 3.

Department of Cardiology, Gunma Prefectural Cardiovascular Center.

Background: The impact of chronic kidney disease (CKD) on long-term outcomes following acute myocardial infarction (AMI) in the era of modern primary PCI with optimal medical therapy is still in debate.Methods and Results:A total of 3,281 patients with AMI were enrolled in the J-MINUET registry, with primary PCI of 93.1% in STEMI. CKD stage on admission was classified into: no CKD (eGFR ≥60 mL/min/1.73 m); moderate CKD (60>eGFR≥30 mL/min/1.73 m); and severe CKD (eGFR <30 mL/min/1.73 m). While the primary endpoint was all-cause mortality, the secondary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, cardiac failure, myocardial infarction (MI) and stroke. Of the 3,281 patients, 1,878 had no CKD, 1,073 had moderate CKD and 330 had severe CKD. Pre-person-days age- and sex-adjusted in-hospital mortality significantly increased from 0.014% in no CKD through 0.042% in moderate CKD to 0.084% in severe CKD (P<0.0001). Three-year mortality and MACE significantly deteriorated from 5.09% and 15.8% in no CKD through 16.3% and 38.2% in moderate CKD to 36.7% and 57.9% in severe CKD, respectively (P<0.0001). C-index significantly increased from the basic model of 0.815 (0.788-0.841) to 0.831 (0.806-0.857), as well as 0.731 (0.708-0.755) to 0.740 (0.717-0.764) when adding CKD stage to the basic model in predicting 3-year mortality (P=0.013; net reclassification improvement [NRI] 0.486, P<0.0001) and MACE (P=0.046; NRI 0.331, P<0.0001) respectively.

Conclusions: CKD remains a useful predictor of in-hospital and 3-year mortality as well as MACE after AMI in the modern PCI and optimal medical therapy era.
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http://dx.doi.org/10.1253/circj.CJ-20-1115DOI Listing
June 2021

Improvements of predictive power of B-type natriuretic peptide on admission by mathematically estimating its discharge levels in hospitalised patients with acute heart failure.

Open Heart 2021 May;8(1)

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Backgrounds: Earlier studies showed that in patients with heart failure (HF), circulating levels of B-type natriuretic peptide (BNP) at hospital discharge (BNP) are more predictive of prognosis than BNP levels on admission (BNP). However, the mechanism underlying that difference has not been fully elucidated. We examined the association between confounding factors during hospitalisation and BNP in patients with HF.

Methods: We identified patients admitted to our hospital for HF (BNP ≥100 pg/mL). Estimated left ventricular end-diastolic pressure (eLVEDP) was calculated using echocardiographic data. To identify the factors associated with the relation between BNP and BNP, we performed a stepwise regression analysis of retrospective data. To validate that analysis, we performed a prospective study.

Results: Through stepwise regression of the patient data (n=688, New York Heart Association 3-4, 88%), we found age, blood urea nitrogen and eLVEDP to be significantly (p<0.05) associated with BNP. Through multivariate analysis after accounting for these factors, we created a formula for predicting BNP levels at discharge (-BNP) from BNP and other parameters measured at admission (p<0.05). By statistically adjusting for these factors, the prognostic power of BNP was significantly improved (p<0.001). The prospective study also confirmed the strong correlation between -BNP and BNP (n=104, r=0.625, p<0.05).

Conclusion: This study showed that statistically accounting for confounding factors affecting BNP levels improves the predictive power of BNP levels measured at the time of hospital admission, suggesting that these confounding factors are associated with lowering predictive power of BNP on admission.

Trial Registration Number: UMIN 000034409, 00035428.
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http://dx.doi.org/10.1136/openhrt-2021-001603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130754PMC
May 2021

Machine learning model for predicting out-of-hospital cardiac arrests using meteorological and chronological data.

Heart 2021 May 17. Epub 2021 May 17.

Department of Preventive Medicine and Epidemiologic Informatics, National Cerebral Cardiovascular Centre, Suita, Japan.

Objectives: To evaluate a predictive model for robust estimation of daily out-of-hospital cardiac arrest (OHCA) incidence using a suite of machine learning (ML) approaches and high-resolution meteorological and chronological data.

Methods: In this population-based study, we combined an OHCA nationwide registry and high-resolution meteorological and chronological datasets from Japan. We developed a model to predict daily OHCA incidence with a training dataset for 2005-2013 using the eXtreme Gradient Boosting algorithm. A dataset for 2014-2015 was used to test the predictive model. The main outcome was the accuracy of the predictive model for the number of daily OHCA events, based on mean absolute error (MAE) and mean absolute percentage error (MAPE). In general, a model with MAPE less than 10% is considered highly accurate.

Results: Among the 1 299 784 OHCA cases, 661 052 OHCA cases of cardiac origin (525 374 cases in the training dataset on which fourfold cross-validation was performed and 135 678 cases in the testing dataset) were included in the analysis. Compared with the ML models using meteorological or chronological variables alone, the ML model with combined meteorological and chronological variables had the highest predictive accuracy in the training (MAE 1.314 and MAPE 7.007%) and testing datasets (MAE 1.547 and MAPE 7.788%). Sunday, Monday, holiday, winter, low ambient temperature and large interday or intraday temperature difference were more strongly associated with OHCA incidence than other the meteorological and chronological variables.

Conclusions: A ML predictive model using comprehensive daily meteorological and chronological data allows for highly precise estimates of OHCA incidence.
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http://dx.doi.org/10.1136/heartjnl-2020-318726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223656PMC
May 2021

Circulating Mature PCSK9 Level Predicts Diminished Response to Statin Therapy.

J Am Heart Assoc 2021 Jun 15;10(11):e019525. Epub 2021 May 15.

Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka Japan.

Background Statin-mediated efficacy of lowering low-density lipoprotein (LDL) cholesterol varies in each individual, and its diminished response is associated with worse outcomes. However, there is no established approach to predict hyporesponse to statins. PCSK9 (proprotein convertase subxilisin/kexin type 9) is a serine-protease associated with LDL metabolism, which circulates as mature and furin-cleaved PCSK9. Since mature PCSK9 more potently degrades the LDL receptor, its evaluation may enable the identification of statin hyporesponders. Methods and Results We analyzed 101 statin-naive patients with coronary artery disease who commenced a statin. PCSK9 subtypes at baseline and 1 month after statin use were measured by ELISA. Hyporesponse to statins was defined as a percent reduction in LDL cholesterol <15%. The relationship between each PCSK9 subtype level and hyporesponse to statins was investigated. Statins significantly lowered LDL cholesterol level (percent reduction, 40%±21%), whereas 11% of study participants exhibited a hyporeseponse to statins. Multivariable logistic regression analysis demonstrated that baseline mature PCSK9 level was an independent predictor for hyporesponse to statins even after adjusting clinical characteristics (mature PCSK9 per 10-ng/mL increase: odds ratio [OR], 1.12; 95% CI, 1.01-1.24 [=0.03]), whereas furin-cleaved level was not (per 10-ng/mL increase: OR, 1.37; 95% CI, 0.73-2.58 [=0.33]). Receiver operating characteristic curve analysis identified mature PCSK9 level of 228 ng/mL as an optimal cutoff to predict hyporesponse to statins (area under the curve, 0.73 [sensitivity, 0.91; specificity, 0.56]). Conclusions Baseline mature PCSK9 level >228 ng/mL is associated with hyporesponse to statins. This finding suggests that mature PCSK9 might be a potential determinant of hyporesponse to statins.
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http://dx.doi.org/10.1161/JAHA.120.019525DOI Listing
June 2021

Long-Term Clinical Impact of Cardiogenic Shock and Heart Failure on Admission for Acute Myocardial Infarction.

Int Heart J 2021 May 15;62(3):520-527. Epub 2021 May 15.

Department of Cardiology, Fukuoka University School of Medicine.

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P < 0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P < 0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.
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http://dx.doi.org/10.1536/ihj.20-646DOI Listing
May 2021

The association between the extent of lipidic burden and delta-fractional flow reserve: analysis from coronary physiological and near-infrared spectroscopic measures.

Cardiovasc Diagn Ther 2021 Apr;11(2):362-372

Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Osaka, Japan.

Background: Vulnerable plaque features including lipidic plaque have been shown to affect fractional flow reserve (FFR). Given that formation and propagation of lipid plaque is accompanied by endothelial dysfunction which impairs vascular tone, the degree of lipidic burden may affect vasoreactivity during hyperemia, potentially leading to reduced FFR. Our aim is to elucidate the relationship of the extent of lipidic plaque burden with coronary physiological vasoreactivity measure.

Methods: We analyzed 89 subjects requeuing PCI due to angiographically intermediate coronary stenosis with FFR ≤0.80. Near-infrared spectroscopy (NIRS) and intravascular ultrasound were used to evaluate lipid-core burden index (LCBI) and atheroma volume at both target lesion (maxLCBI; maximum value of LCBI within any 4 mm segments) and entire target vessel (LCBI: LCBI within entire vessel). In addition to FFR, delta-FFR was measured by difference of distal coronary artery pressure/aortic pressure (Pd/Pa) between baseline and hyperemic state.

Results: The averaged FFR and delta-FFR was 0.74 (0.69-0.77), and 0.17±0.05, respectively. On target lesion-based analysis, maxLCBI was negatively correlated to FFR (ρ=-0.213, P=0.040), and it was positively correlated to delta-FFR (ρ=0.313, P=0.002). Furthermore, target vessel-based analysis demonstrated similar relationship of LCBI with FFR (ρ=-0.302, P=0.003) and delta-FFR (ρ=0.369, P<0.001). Even after adjusting clinical characteristics and lesion/vessel features, delta-FFR (by 0.10 increase) was independently associated with maxLCBI (β=57.2, P=0.027) and LCBI (β=24.8, P=0.007) by mixed linear model analyses.

Conclusions: A greater amount of lipidic plaque burden at not only "target lesion" alone but "entire target vessel" was associated with a greater delta-FFR. The accumulation of lipidic plaque materials at both local site and entire vessel may impair hyperemia-induced vasoreactivity, which causes a reduced FFR.
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http://dx.doi.org/10.21037/cdt-20-1024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102241PMC
April 2021

Validation of the atherothrombotic risk score for secondary prevention in patients with acute myocardial infarction: the J-MINUET study.

Heart Vessels 2021 Oct 21;36(10):1506-1513. Epub 2021 Apr 21.

Department of Cardiology, Gunma Prefectural Cardiovascular Center, Maebashi, Japan.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS2°P) is a contemporary risk scoring system for secondary prevention based on nine clinical factors. However, this scoring system has not been validated in other populations. The aim of this study was to validate the TRS2°P in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI) in a nationwide registry cohort. Among 3283 consecutive patients with AMI enrolled in the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET), a total of 2611 patients who underwent primary PCI were included in this study. The performance of the TRS2°P to predict major adverse cardiovascular events (MACE) composed of all-cause death, non-fatal MI, and non-fatal stroke up to 3 years in the present cohort was evaluated. The TRS2°P had modest discriminative performance in this J-MINUET cohort with a c-statistic of 0.63, similar to that in the derived cohort (TRA2°P-TIMI50, c-statistic 0.67). A strong graded relationship between the TRS2°P and 3-year cardiovascular event rates was also observed in the J-MINUET cohort. Age ≥ 75 years, Killip ≥ 2, prior stroke, peripheral artery disease, anemia, and non-ST-elevation myocardial infarction were identified as independent factors for the incidence of MACE. The TRS2°P modestly predicted secondary cardiovascular events among patients with AMI treated by primary PCI in a nationwide cohort of Japan. Further studies are needed to develop a novel risk score better predicting secondary cardiovascular events.
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http://dx.doi.org/10.1007/s00380-021-01840-zDOI Listing
October 2021

Clinical Characteristics and Outcomes of Hospitalized Patients With Heart Failure From the Large-Scale Japanese Registry Of Acute Decompensated Heart Failure (JROADHF).

Circ J 2021 Aug 15;85(9):1438-1450. Epub 2021 Apr 15.

Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University.

Background: With aging population, the prevalence and incidence of heart failure (HF) have been increasing worldwide. However, the characteristics and outcomes of patients with HF in an era of aging are not well established in Japan.Methods and Results:The Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter, nationwide registry, was designed to study the clinical characteristics and outcomes of patients hospitalized with HF throughout Japan in 2013. One hundred and twenty-eight hospitals were selected by cluster random sampling and 13,238 hospitalized patients with HF were identified by medical record review. Demographics, medical history, severity, treatment, and in-hospital and long-term outcome data were collected from the Diagnostic Procedure Combination and medical charts. Data were analyzed using univariate and multivariate logistic regression or Cox regression analysis. The mean age of registered patients was 78.0±12.5 years and 52.8% were male. Elderly patients (age >75 years) accounted for 68.9%, and HF with preserved ejection fraction (HFpEF) accounted for 45.1%. Median length of hospital stay was 18 days and in-hospital mortality was 7.7%. The median follow-up period was 4.3 years, and the incidence rates for cardiovascular death and rehospitalization for HF were 7.1 and 21.1 per 100 person-years, respectively.

Conclusions: A contemporary nationwide registry demonstrated that hospitalized HF patients were very elderly, HFpEF was common, and their prognosis was still poor in Japan.
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http://dx.doi.org/10.1253/circj.CJ-20-0947DOI Listing
August 2021

Accessory pathway analysis using a multimodal deep learning model.

Sci Rep 2021 Apr 13;11(1):8045. Epub 2021 Apr 13.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Hospital, 7-5-2, Kusunoki-Cho, Chuo-Ku, Kobe, Japan.

Cardiac accessory pathways (APs) in Wolff-Parkinson-White (WPW) syndrome are conventionally diagnosed with decision tree algorithms; however, there are problems with clinical usage. We assessed the efficacy of the artificial intelligence model using electrocardiography (ECG) and chest X-rays to identify the location of APs. We retrospectively used ECG and chest X-rays to analyse 206 patients with WPW syndrome. Each AP location was defined by an electrophysiological study and divided into four classifications. We developed a deep learning model to classify AP locations and compared the accuracy with that of conventional algorithms. Moreover, 1519 chest X-ray samples from other datasets were used for prior learning, and the combined chest X-ray image and ECG data were put into the previous model to evaluate whether the accuracy improved. The convolutional neural network (CNN) model using ECG data was significantly more accurate than the conventional tree algorithm. In the multimodal model, which implemented input from the combined ECG and chest X-ray data, the accuracy was significantly improved. Deep learning with a combination of ECG and chest X-ray data could effectively identify the AP location, which may be a novel deep learning model for a multimodal model.
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http://dx.doi.org/10.1038/s41598-021-87631-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044112PMC
April 2021

Validation of Acute Myocardial Infarction and Heart Failure Diagnoses in Hospitalized Patients With the Nationwide Claim-Based JROAD-DPC Database.

Circ Rep 2021 Feb 20;3(3):131-136. Epub 2021 Feb 20.

Department of Cardiovascular Medicine, Tohoku University Hospital, Tohoku University Graduate School of Medicine Sendai Japan.

Big data systems such as diagnosis procedure combination (DPC) datasets have recently been used for research purposes. However, there have been few validation studies to determine the accuracy of diagnoses. The aim of this study was to validate and evaluate 2 diagnoses, namely acute myocardial infarction (AMI) and heart failure (HF), using International Classification of Diseases, 10th revision (ICD-10) codes in the Japanese Registry Of All cardiac and vascular Disease (JROAD)-DPC database. ICD-10 codes I21.0-I21.9 and I50.0-I50.9 were used to identify AMI and HF, respectively, in the JROAD-DPC database. Diagnoses of AMI and HF were validated in clinical datasets assessing sensitivity and positive predictive value (PPV). Over 1-2 years, 742 patients hospitalized for AMI and 1,368 patients hospitalized for HF were identified in the DPC dataset. Sensitivity and PPV for AMI were 78.9% and 78.8%, respectively. When emergency hospitalization was included as a criterion, PPV increased to 84.9%. For HF, sensitivity and PPV were 84.7% and 57.0%, respectively. When emergency hospitalization and acute HF were included as criteria, PPV increased to 83.0%. Using ICD-10 codes for AMI and HF diagnoses among hospitalized patients, the DPC dataset showed acceptable concordance with clinical datasets. PPV increased when any conditions of hospitalization were included, especially in HF.
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http://dx.doi.org/10.1253/circrep.CR-21-0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956876PMC
February 2021

The feasibility and limitation of coronary computed tomographic angiography imaging to identify coronary lipid-rich atheroma in vivo: Findings from near-infrared spectroscopy analysis.

Atherosclerosis 2021 04 24;322:1-7. Epub 2021 Feb 24.

Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Background: Coronary computed tomography angiography (CCTA) non-invasively visualizes lipid-rich plaque. However, this ability is not fully validated in vivo. The current study aimed to elucidate the association of CCTA features with near-infrared spectroscopy-derived lipidic plaque measure in patients with coronary artery disease.

Methods: 95 coronary lesions (culprit/non-culprit = 51/44) in 35 CAD subjects were evaluated by CCTA and NIRS imaging. CT density, positive remodeling, spotty calcification, napkin-ring sign and NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI) were analyzed by two independent physicians. The association of CCTA-derived plaque features with maxLCBI ≥ 400 was evaluated.

Results: The median CT density and maxLCBI were 57.7 Hounsfield units (HU) and 304, respectively. CT density (r = -0.75, p < 0.001) and remodeling index (RI) (r = 0.58, p < 0.001) were significantly associated with maxLCBI, respectively. Although napkin-ring sign (p < 0.001) showed higher prevalence of maxLCBI ≥ 400 than those without it, spotty calcification did not (p = 0.13). On multivariable analysis, CT density [odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.93-0.97; p < 0.001] and positive remodeling [OR = 7.71, 95%CI = 1.37-43.41, p = 0.02] independently predicted maxLCBI ≥ 400. Receiver operating characteristic curve analysis demonstrated CT density <32.9 HU (AUC = 0.92, sensitivity = 85.7%, specificity = 91.7%) and RI ≥ 1.08 (AUC = 0.83, sensitivity = 74.3%, specificity = 85.0%) as optimal cut-off values of maxLCBI ≥ 400. Of note, only 52.6% at lesions with one of these plaque features exhibited maxLCBI ≥ 400, whereas the frequency of maxLCBI ≥ 400 was highest at those with both features (88.5%, p < 0.001 for trend).

Conclusions: CT density <32.9 HU and RI ≥ 1.08 were associated with lipid-rich plaque on NIRS imaging. Our findings underscore the synergistic value of CT density and positive remodeling to detect lipid-rich plaque by CCTA.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.02.019DOI Listing
April 2021

Estimating Incidence of Acute Heart Failure Syndromes in Japan - An Analysis From the KUNIUMI Registry.

Circ J 2021 Mar 5. Epub 2021 Mar 5.

Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine.

Background: Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055.

Conclusions: The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.
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http://dx.doi.org/10.1253/circj.CJ-20-1154DOI Listing
March 2021

Institutional Characteristics and Prognosis of Acute Myocardial Infarction With Cardiogenic Shock in Japan - Analysis From the JROAD/JROAD-DPC Database.

Circ J 2021 Mar 4. Epub 2021 Mar 4.

Department of Cardiovascular Medicine, Kyushu University.

Background: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients.Methods and Results:In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%.

Conclusions: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.
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http://dx.doi.org/10.1253/circj.CJ-20-0655DOI Listing
March 2021

Prognostic comparison of atrial and ventricular functional mitral regurgitation.

Open Heart 2021 02;8(1)

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Objective: Atrial functional mitral regurgitation (A-FMR) has been suggested as a new aetiology of functional MR (MR); however, its prognosis and prognostic predictors are not fully elucidated. Aim of this study was to investigate the prognosis and prognostic predictors of A-FMR in comparison with ventricular functional MR (V-FMR).

Methods: Three hundred and seventy-eight consecutive patients with moderate-to-severe or severe functional MR were studied. Functional MR was classified into V-FMR (N=288) and A-FMR (N=90) depending on the alterations of left ventricle (LV) or left atrium (LA) along with clinical context and diagnosis of ischaemic heart disease or cardiomyopathy.

Results: During a median follow-up of 4.1 (2.0-6.7) years, all-cause mortality, cardiovascular mortality and heart failure (HF) hospitalisation occurred in 98 (26%), 81 (21%) and 177 (47%) patients, respectively, and rates of these events and the composite end point of all-cause mortality and HF hospitalisation were consistently higher in V-FMR than A-FMR (unadjusted HR 1.762 (95% CI 1.250 to 2.438), p<0.001; adjusted HR 1.654 (95% CI 1.027 to 2.664), p=0.038, for the composite end point). Further analysis showed different prognostic predictors between V-FMR and A-FMR; while age and LA volume index were independent prognostic predictors of both V-FMR and A-FMR, systolic blood pressure and B-type natriuretic peptide were also those of V-FMR, and estimated glomerular filtration rate, LV end-systolic dimension and tricuspid regurgitation were also those of A-FMR.

Conclusions: The prognosis of V-FMR was significantly worse than that of A-FMR, and prognostic predictors were different between V-FMR and A-FMR. Our study suggests the importance of discriminating A-FMR and V-FMR, and that different treatment strategies may be considered for each aetiology.
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http://dx.doi.org/10.1136/openhrt-2021-001574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887352PMC
February 2021

Information retrieval on oncology knowledge base using recursive paraphrase lattice.

J Biomed Inform 2021 04 11;116:103705. Epub 2021 Feb 11.

Xcoo, Inc., Mitsuyama Bldg., 4F, 4-2-5, Hongo, Bunkyo-ku, Tokyo, Japan. Electronic address:

For annotation in cancer genomic medicine, oncologists have to refer to various knowledge bases worldwide and retrieve all information (e.g., drugs, clinical trials, and academic papers) related to a gene variant. However, oncologists find it difficult to search these knowledge bases comprehensively because there are multiple paraphrases containing abbreviations and foreign languages in their terminologies including diseases, drugs, and genes. In this paper, we propose a novel search method considering deep paraphrases, which helps oncologists retrieve essential annotation resources swiftly and effortlessly. Our method recursively finds paraphrases based on paraphrase corpora, expands a source document, and finally generates a paraphrase lattice. The proposed method also feedbacks beneficial information regarding the paraphrases applied for a search, which is useful for selecting search results and considering a query for the succeeding search. The results of an experiment demonstrated that our method could retrieve important annotation information that could not be retrieved using a conventional search system and simple paraphrasing. Additionally, annotation experts evaluated our method and found it to be practical.
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http://dx.doi.org/10.1016/j.jbi.2021.103705DOI Listing
April 2021

COVID-19 pandemic is associated with mechanical complications in patients with ST-elevation myocardial infarction.

Open Heart 2021 02;8(1)

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Objective: Although there are regional reports that the COVID-19 pandemic is associated with a reduction in acute myocardial infarction presentations and primary percutaneous coronary intervention (PCI) procedures, little is known about the impact of the COVID-19 pandemic on mechanical complications resulting from ST-segment elevation myocardial infarction (STEMI) and mortality.

Methods: This single-centre retrospective cohort study analysed presentations, incidence of mechanical complications, and mortality in patients with STEMI before and after a state of emergency was declared due to the COVID-19 pandemic by the Japanese government on 7 April 2020.

Results: We analysed 359 patients with STEMI hospitalised before the declaration and 63 patients hospitalised after the declaration. The proportion of patients with late presentation was significantly higher after the declaration than before (25.4% vs 14.2%, p=0.03). The incidence of late presentation was significantly higher during the COVID-19 pandemic than before (incidence rate ratio (IRR), 2.41; 95% CI, 1.37 to 4.05; p=0.001, even after adjusting for month (IRR, 2.61; 95% CI, 1.33 to 5.13; p<0.01). Primary PCI was performed significantly less often after the declaration than before (68.3% vs 82.5%, p=0.009). The mechanical complication resulting from STEMI occurred in 13 of 359 (3.6%) patients before the declaration and 9 of 63 (14.3%) patients after the declaration (p<0.001). However, the incidence of in-hospital death (before, 6.2% vs after, 6.4%, p=0.95) was comparable.

Conclusions: Following the COVID-19 pandemic, an increased incidence of mechanical complications resulting from STEMI was observed. Instructing people to stay at home, without effectively educating them to immediately seek medical attention when suffering symptoms of a heart attack, may worsen outcomes in patients with STEMI.
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http://dx.doi.org/10.1136/openhrt-2020-001497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871043PMC
February 2021

Patients With and Gene Variants Experienced Higher Incidence of Cardiovascular Outcomes in Heterozygous Familial Hypercholesterolemia.

J Am Heart Assoc 2021 02 3;10(4):e018263. Epub 2021 Feb 3.

Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Suita Osaka Japan.

Background Patients with familial hypercholesterolemia who harbored both low-density lipoprotein receptor () and (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low-density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both and gene variants. Methods and Results A total of 232 unrelated patients with and/or gene variants were stratified as follows: patients with and () gene variants, patients with gene variant, and patients with gene variant. Clinical demographics and the occurrence of primary outcome (nonfatal myocardial infarction) were compared. The observation period of primary outcome started at the time of birth and ended at the time of the first cardiac event or the last visit. Patients with gene variants were identified in 6% of study patients. They had higher levels of low-density lipoprotein cholesterol (=0.04) than those with gene variants. On multivariate Cox regression model, they experienced a higher incidence of nonfatal myocardial infarction (hazard ratio, 4.62; 95% CI, 1.66-11.0; =0.003 versus patients with gene variant). Of note, risk for nonfatal myocardial infarction was greatest in male patients with gene variants compared with those with gene variant (86% versus 24%; <0.001). Conclusions Patients with gene variants were high-risk genotype associated with atherogenic lipid profiles and worse cardiovascular outcomes. These findings underscore the importance of genetic testing to identify patients with gene variants, who require more stringent antiatherosclerotic management.
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http://dx.doi.org/10.1161/JAHA.120.018263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955325PMC
February 2021

Current practice and effects of intravenous anticoagulant therapy in hospitalized acute heart failure patients with sinus rhythm.

Sci Rep 2021 01 13;11(1):1202. Epub 2021 Jan 13.

Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

Although the risk of thromboembolism is increased in heart failure (HF) patients irrespective of atrial fibrillation (AF), especially during the acute decompensated phase, the effects of intravenous anticoagulants for these patients remain unclear. We sought to investigate the current practice and effects of intravenous anticoagulant therapy in acute HF (AHF) patients with sinus rhythm. We analyzed a nationwide prospective cohort from April 2012 to March 2016. We extracted 309,015 AHF adult patients. After application of the exclusion criteria, we divided the 92,573 study population into non-heparin [n = 70,621 (76.3%)] and heparin [n = 21,952 (23.7%)] groups according to the use of intravenous heparin for the first 2 consecutive days after admission. Multivariable logistic regression analyses demonstrated that heparin administration was not associated with in-hospital mortality (OR 0.97, 95% CI 0.91-1.03) and intracranial hemorrhage (OR 1.18, 95% CI 0.78-1.77), while heparin administration was significantly associated with increased incidence of ischemic stroke (OR 1.49, 95% CI 1.29-1.72) and venous thromboembolism (OR 1.62, 95% CI 1.14-2.30). In conclusion, intravenous heparin administration was not associated with favorable in-hospital outcomes in AHF patients with sinus rhythm. Routine additive use of intravenous heparin to initial treatment might not be recommended in AHF patients.
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http://dx.doi.org/10.1038/s41598-020-79700-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807069PMC
January 2021

Anesthesia for Cesarean Section and Postpartum Cardiovascular Events in Congenital Heart Disease: A Retrospective Cohort Study.

J Cardiothorac Vasc Anesth 2021 Jul 24;35(7):2108-2114. Epub 2020 Nov 24.

Department of Anesthesiology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Objective: To clarify the association between anesthetic technique and maternal and neonatal outcomes in parturients with congenital heart disease (CHD).

Design: Retrospective, observational cohort study.

Setting: An academic hospital.

Participants: A total of 263 consecutive parturients with CHD who underwent cesarean section from 1994 to 2019.

Interventions: None.

Measurements And Main Results: The authors compared postpartum cardiovascular events (composite of heart failure, pulmonary hypertension, arrhythmia, and thromboembolic complications) and neonatal outcomes (intubation and Apgar score <7 at one or five minutes) by anesthetic technique. Among 263 cesarean sections, general anesthesia was performed in 47 (17.9%) parturients and neuraxial anesthesia in 214 (81.3%) parturients. Cardiovascular events were more common in the general anesthesia group (n = 7; 14.9%) than in the neuraxial anesthesia group (n = 17; 7.9%). Generalized linear mixed models assuming a binomial distribution (ie, mixed-effects logistic regression), with a random intercept for each modified World Health Organization classification for maternal cardiovascular risk, revealed that general anesthesia was not significantly associated with cardiovascular events (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.30-3.29). In addition, general anesthesia was associated with composite neonatal outcomes (Apgar score <7 at one or five minutes or need for neonatal intubation; OR, 13.3; 95% CI, 5.52-32.0).

Conclusion: Anesthetic technique is not significantly associated with postpartum composite cardiovascular events. General anesthesia is significantly associated with increased need for neonatal intubation and lower Apgar scores.
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http://dx.doi.org/10.1053/j.jvca.2020.11.042DOI Listing
July 2021
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