Publications by authors named "Issei Komuro"

1,041 Publications

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Promoting analysis of real-world data: Prospects for preventive cardiology in Japan.

Glob Health Med 2021 Aug;3(4):203-213

Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

According to the statistics for 2018 in Japan, cardiovascular disease and cerebrovascular disease were the most common causes of death (cardiovascular disease with 208,210, cerebrovascular disease with 108,165), and these two diseases account for 23.2% of all deaths. Stroke, especially cerebral hemorrhage, was the main cause of death in Japan after World War II. Along with improved management of hypertension, the mortality rate from cerebral hemorrhage reached a high of 266.7 per 100,000 men in 1960 and 213.9 per 100,000 women in 1951, then decreased to 15.9 per 100,000 men and 6.9 per 100,000 women in 2013. However, mortality from lifestyle-related diseases such as metabolic syndrome and ischemic heart disease has been on the rise since 1990 due to the westernization of diet, urban lifestyles, and lack of exercise habits. Moreover, since aging is the greatest risk factor for heart failure, the number of patients with heart failure in Japan will inevitably increase in the future. A large amount of evidence has demonstrated that prevention and proper management of risk factors can reduce the future incidence of cardiovascular disease. Specific health checkups (metabolic syndrome checkups) have been carried out in Japan since 2008. Big data on physical examinations are valuable real-world data that can be utilized for clinical research. As the importance of preventive cardiology increases in the future, we should analyze the real-world data from health checkups in Japan in detail and disseminate these results to clinical practice, which will contribute to development of preventive cardiology and the promotion of public health.
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http://dx.doi.org/10.35772/ghm.2020.01077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403265PMC
August 2021

Efficacy of intensive lipid-lowering therapy with statins stratified by blood pressure levels in patients with type 2 diabetes mellitus and retinopathy: Insight from the EMPATHY study.

Hypertens Res 2021 Sep 15. Epub 2021 Sep 15.

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

Intensive lipid-lowering therapy is recommended in individuals exhibiting type 2 diabetes mellitus (T2DM) with microvascular complications (as high-risk patients), even without known cardiovascular disease (CVD). However, evidence is insufficient to stratify the patients who would benefit from intensive therapy among them. Hypertension is a major risk factor, and uncontrolled blood pressure (BP) is associated with increased CVD risk. We evaluated the efficacy of intensive vs. standard statin therapy for primary CVD prevention among T2DM patients with retinopathy stratified by BP levels. We used the dataset from the EMPATHY study, which compared intensive statin therapy targeting low-density lipoprotein cholesterol (LDL-C) levels of <70 mg/dL and standard therapy targeting LDL-C levels ranging from ≥100 to <120 mg/dL in T2DM patients with retinopathy without known CVD. A total of 4980 patients were divided into BP ≥ 130/80 mmHg (systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg, n = 3335) and BP < 130/80 mmHg (n = 1645) subgroups by baseline BP levels. During the median follow-up of 36.8 months, 281 CVD events were observed. Consistent with previous studies, CVD events occurred more frequently in the BP ≥ 130/80 mmHg subgroup than in the BP < 130/80 mmHg subgroup (P < 0.001). In the BP ≥ 130/80 mmHg subgroup, intensive statin therapy was associated with lower CVD risk (HR 0.70, P = 0.015) than standard therapy after adjustment. No such association was observed in the BP < 130/80 mmHg subgroup. The interaction between BP subgroup and statin therapy was significant. In conclusion, intensive statin therapy targeting LDL-C < 70 mg/dL provided benefits in primary CVD prevention when compared with standard therapy among T2DM patients with retinopathy and BP ≥ 130/80 mmHg.
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http://dx.doi.org/10.1038/s41440-021-00734-xDOI Listing
September 2021

Practical Assessment of the Tradeoff between Fatal Bleeding and Coronary Thrombotic Risks using the Academic Research Consortium for High Bleeding Risk Criteria.

J Atheroscler Thromb 2021 Sep 15. Epub 2021 Sep 15.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.

Aims: We aimed to establish a practical method for the assessment of tradeoff between thrombotic and bleeding risks.

Methods: We aimed to investigate the balance between bleeding risk and coronary thrombotic risk according to the number of the Academic Research Consortium for high bleeding risk (ARC-HBR) criteria in the multicenter prospective ST/non-ST elevation myocardial infarction (STEMI/NSTEMI) registry (N=12,093). Patients were divided as follows by the number of ARC-HBR criteria fulfilled: group 0, 0 major with ≤ 1 minor (N=6,792); group 1, 1 major with 0 minor (N=1,705); group 2, 0 major with ≥ 2 minors (N=790); group 3, 1 major with ≥ 1 minor (N=1,709); group 4, 2 majors with ≥ 0 minors (N=861); and group 5, ≥ 3 majors with ≥ 0 minor (N=236). We assessed the acute-phase absolute risk differences between bleeding and coronary thrombotic events in each group.

Results: At 7-day follow-up, all patients (groups 0-5) had a higher risk of major bleeding than that of any myocardial infarction (MI). Patients at ARC-HBR (groups 1-5) had a balanced risk between fatal MI and fatal bleeding, whereas patients at non-ARC-HBR (group 0) had a higher risk of fatal MI than that of fatal bleeding.

Conclusions: All STEMI/NSTEMI patients have a relatively high risk of major bleeding as compared with the risk of any MI in the acute phase. The ARC-HBR criteria would be a practical tool for assessing the tradeoff between fatal bleeding and fatal MI risks. This practical assessment would be helpful for the optimal decision-making of appropriate treatment strategy considering the balance between bleeding and coronary thrombotic risks.
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http://dx.doi.org/10.5551/jat.62999DOI Listing
September 2021

Characteristics and in-hospital outcomes of patients undergoing balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: a time-trend analysis from the Japanese nationwide registry.

Open Heart 2021 Sep;8(2)

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Background: Balloon pulmonary angioplasty (BPA), a novel technique initially introduced as a treatment for inoperable chronic thromboembolic pulmonary hypertension, is now increasingly being performed in a broader spectrum of patients. Here, we performed a time-trend analysis of the characteristics and in-hospital outcomes of patients who underwent BPA in Japan, using data extracted from nationwide procedure-based registration system.

Methods: The Japanese Structural Heart Disease (J-SHD) registry was established and sponsored by the Japanese Association of Cardiovascular Intervention and Therapeutics and aims to provide basic statistics on the performance of structural interventions in Japan. J-SHD registers cases from approximately 200 institutions, representing more than 90% of SHD intervention-performing hospitals in the nation. We analysed the registered BPA data elements from January 2015 to December 2018. Successful BPA was defined as a session in which a physician successfully treated all targeted lesions.

Results: There were a total of 2512 BPA sessions; the number of institutions and registered sessions increased from 30 to 50 sites and from 479 to 852 sessions during the study period, respectively. The average age of the patients was 66±13 years, and 72.1% were women. In-hospital death was observed in 0.2%, and the total complications rate was 5.3%. The preoperative and postoperative mean pulmonary artery pressure were 32±11 mm Hg and 30±10 mm Hg, respectively.

Conclusion: The number of BPA sessions increased during the study period, with an acceptable in-hospital complication rate.
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http://dx.doi.org/10.1136/openhrt-2021-001721DOI Listing
September 2021

External validation of the 4C Mortality Score for patients with COVID-19 and pre-existing cardiovascular diseases/risk factors.

BMJ Open 2021 09 8;11(9):e052708. Epub 2021 Sep 8.

Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan

Objectives: Predictive algorithms to inform risk management decisions are needed for patients with COVID-19, although the traditional risk scores have not been adequately assessed in Asian patients. We aimed to evaluate the performance of a COVID-19-specific prediction model, the 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score, along with other conventional critical care risk models in Japanese nationwide registry data.

Design: Retrospective cohort study.

Setting And Participants: Hospitalised patients with COVID-19 and cardiovascular disease or coronary risk factors from January to May 2020 in 49 hospitals in Japan.

Main Outcome Measures: Two different types of outcomes, in-hospital mortality and a composite outcome, defined as the need for invasive mechanical ventilation and mortality.

Results: The risk scores for 693 patients were tested by predicting in-hospital mortality for all patients and composite endpoint among those not intubated at baseline (n=659). The number of events was 108 (15.6%) for mortality and 178 (27.0%) for composite endpoints. After missing values were multiply imputed, the performance of the 4C Mortality Score was assessed and compared with three prediction models that have shown good discriminatory ability (RISE UP score, A-DROP score and the Rapid Emergency Medicine Score (REMS)). The area under the receiver operating characteristic curve (AUC) for the 4C Mortality Score was 0.84 (95% CI 0.80 to 0.88) for in-hospital mortality and 0.78 (95% CI 0.74 to 0.81) for the composite endpoint. It showed greater discriminatory ability compared with other scores, except for the RISE UP score, for predicting in-hospital mortality (AUC: 0.82, 95% CI 0.78 to 0.86). Similarly, the 4C Mortality Score showed a positive net reclassification improvement index over the A-DROP and REMS for mortality and over all three scores for the composite endpoint. The 4C Mortality Score model showed good calibration, regardless of outcome.

Conclusions: The 4C Mortality Score performed well in an independent external COVID-19 cohort and may enable appropriate disposition of patients and allocation of medical resources. UMIN000040598.
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http://dx.doi.org/10.1136/bmjopen-2021-052708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438580PMC
September 2021

Semiquantitative assessed proteinuria and risk of heart failure: Analysis of a nationwide epidemiological database.

Nephrol Dial Transplant 2021 Sep 7. Epub 2021 Sep 7.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Background: Heart failure (HF) is increasing in prevalence worldwide. We explored whether adults with trace and positive proteinuria were at a high risk for incident HF compared with those with negative proteinuria using a nationwide epidemiological database.

Methods: This is an obserevational cohort study using the JMDC Claims Database collected between 2005 and 2020. This is a population-based sample (n = 1,021,943; median age [interquartile range], 44 [37-52] years; 54.8% men). No participants had a known history of cardiovascular disease. Each participant was categorized into three groups according to the urine dipstick test results: negative proteinuria (n = 902,273), trace proteinuria (n = 89,599), and positive proteinuria (≥1+) (n = 30,071). The primary outcome was HF. The secondary outcomes were myocardial infarction, stroke, and atrial fibrillation. We performed multivariable Cox regression analyses to identify the association between the proteinuria category and incient HF and other cardiovascular disease events.

Results: Over a mean follow-up of 1,150 ± 920 days, 17,182 incident HF events occurred. After multivariable adjustment, hazard ratios (HRs) for HF events were 1.09 (95% confidence interval [CI], 1.03-1.15) and 1.59 (95% CI, 1.49-1.70) for trace proteinuria and positive proteinuria vs. negative proteinuria, respectively. This association was present irrespective of clinical characteristics. A stepwise increase in the risk of myocardial infarction, stroke, and atrial fibrillation with proteinuria category was also observed. Our primary results were confirmed in participants after multiple imputation for missing values and in those having no medications for hypertension, diabetes mellitus, and dyslipidemia. Discriminative predictive value for HF events improved by adding the results of urine dipstick test to traditional risk factors (net reclassification improvement 0.0497, 95% CI 0.0346-0.0648, p < 0.001).

Conclusions: Not only positive proteinuria but also trace proteinuria was associated with a greater incidence of HF in the general population. Semiquantitative assessment of proteinuria would be informative for the risk stratification of HF.
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http://dx.doi.org/10.1093/ndt/gfab248DOI Listing
September 2021

Relation of the Metabolic Syndrome to Incident Colorectal Cancer in Young Adults Aged 20 to 49 Years.

Am J Cardiol 2021 Sep 1. Epub 2021 Sep 1.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Onco-cardiology is the emerging field, and the concept of shared risk factor holds an important position in this field. The increasing prevalence of colorectal cancer (CRC) in young adults is a critical epidemiological issue. Although metabolic syndrome, which is a major risk factor for cardiovascular disease, is known to be associated with CRC incidence in middle-aged and elderly individuals, it is unclear whether this association is present in young adults. We assessed whether metabolic syndrome was associated with CRC events in young adults (aged <50 years), and whether the association differed by the definition of metabolic syndrome. We retrospectively analyzed 902,599 adults (20 to 49 years of age) enrolled in the JMDC Claims Database which is a nationwide epidemiological database in Japan between January 2005 and August 2018. Participants who had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Study participants were categorized into 2 groups according to the presence of metabolic syndrome, defined using the Japanese criteria (waist circumference ≥85 cm for men and ≥90 cm for women, and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). Clinical outcomes were collected between January 2005 and August 2018. The primary outcome was CRC of any stage. Median (interquartile range) age was 41 (37 to 45), and 55.4% were men. Over a median follow-up of 1,008 (429 to 1,833) days, there were 1,884 incidences of CRC. After multivariable adjustment, the hazard ratio (HR) of metabolic syndrome for CRC events was 1.26 (95% confidence interval [CI] = 1.07 to 1.49). Cox regression analysis after multiple imputation for missing values showed that metabolic syndrome was associated with CRC incidence (HR = 1.35, 95% CI = 1.17 to 1.56). Metabolic syndrome was also associated with a higher incidence of CRC in individuals with a follow-up period of ≥365 days (HR = 1.33, 95% CI = 1.10 to 1.60). This association was observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.30, 95% CI = 1.09 to 1.55) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.39, 95% CI = 1.12 to 1.72). In conclusion, metabolic syndrome was associated with a higher incidence of CRC among individuals aged <50 years. These results could be informative for risk stratification of subsequent CRC among young adults.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.049DOI Listing
September 2021

Clinical Outcome of Closure of a Small Atrial Septal Defect in a Patient with Pulmonary Arterial Hypertension.

Intern Med 2021 Aug 31. Epub 2021 Aug 31.

Division for Health Service Promotion, The University of Tokyo, Japan.

The closure of small/coincidental atrial septal defects (ASDs) in patients with pulmonary arterial hypertension (PAH) has been described in recent major guidelines as useless or even contraindicated. We confirm the effectiveness of "Treat and Repair" for ASD closure through one patient diagnosed with idiopathic PAH with small ASD, under careful observation with right heart catheterization and cardiac magnetic resonance imaging. The clinical decision concerning the closure of ASD with PAH should be made not only by referring to the guidelines but also by evaluating the benefits and risks specific to that case.
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http://dx.doi.org/10.2169/internalmedicine.7888-21DOI Listing
August 2021

Acute-phase initiation of cardiac rehabilitation and clinical outcomes in hospitalized patients for acute heart failure.

Int J Cardiol 2021 Oct 27;340:36-41. Epub 2021 Aug 27.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Background: Extensive data support the clinical benefit of cardiac rehabilitation (CR) for patients with chronic heart failure (HF). However, whether CR could be beneficial for patients hospitalized for acute heart failure remains unclear.

Methods: We retrospectively analyzed data from the Diagnosis Procedure Combination database, a nationwide inpatient database. We included patients hospitalized for HF, who were aged ≥20 years and with New York Heart Association class ≥II, between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those undergoing major procedures under general anesthesia, those requiring advanced mechanical supports within 2 days after admission, and those with disturbance of consciousness. Propensity score matching and instrumental variable analyses were conducted to compare clinical outcomes between the patients with and without acute-phase initiation of CR defined as initiation of CR within two days after hospital admission.

Results: Among 430,216 eligible patients, 63,470 patients (14.8%) received the acute-phase initiation of CR. Propensity score matching created 63,470 pairs and found that the acute-phase initiation of CR was associated with lower in-hospital mortality (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.73-0.80), shorter hospital stay and lower incidence of 30-day readmission due to HF. The instrumental variable analysis also showed patients with acute-phase initiation of CR was associated with lower in-hospital mortality than those without (OR, 0.73; 95% CI, 0.68-0.79).

Conclusion: Our analysis suggested a potential benefit of acute-phase initiation of CR for short-term clinical outcomes in hospitalized patients with acute HF.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.041DOI Listing
October 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

Efficacy and safety of remote cardiac rehabilitation in the recovery phase of cardiovascular diseases: A protocol paper.

JMIR Res Protoc 2021 Aug 18. Epub 2021 Aug 18.

Kansai Medical University, Osaka, JP.

Background: Conventional group-based outpatient cardiac rehabilitation through monitoring and center-based approaches for patients in the recovery phase has shown strong evidence for the prevention of cardiovascular diseases. However, there are some cases in which maintaining attendance of center-based cardiac rehabilitation is difficult.

Objective: This study aims to ascertain the safety and efficacy of remote cardiac rehabilitation (RCR) in the recovery phase in patients with cardiovascular disease.

Methods: Patients satisfying the study criteria will be recruited from multiple institutions (approximately 30) across Japan. Seventy-five patients (approximately two or three patients from each institution) are proposed to be recruited. To patients enrolled in the RCR group, devices necessary for RCR (calibrated ergometers and tablets) will be lent. Patients will perform anaerobic exercise at home using ergometer for 30-40 minutes at least three times weekly. During exercise, an instructor will monitor the patient in real time (using interactive video tools and monitoring tools for various vital data). Moreover, educational instructions will be given three times weekly using e-learning methods.

Results: The primary endpoint is the peak oxygen uptake 2-3 months from the start of exercise or 6 min walk test. The extracted data will be compared between RCR patients and controls without RCR. This study was funded in December 2020 and received ethical approval in January 2021, and recruitment began in January 2021. 59 study patients had been recruited by March 2021.

Conclusions: The establishment of the system of RCR proposed in this study will lead to the development of more extensive applications, which have been insufficient with conventional interventions.

Clinicaltrial: Clinical Trials Registry (UMIN-CTR; UMIN000042942).
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http://dx.doi.org/10.2196/30725DOI Listing
August 2021

Harmonization of Cardiovascular and Oncology and the Blossoming of Cardio-Oncology in Japan.

JACC CardioOncol 2020 Dec 15;2(5):819-821. Epub 2020 Dec 15.

Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan.

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http://dx.doi.org/10.1016/j.jaccao.2020.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352219PMC
December 2020

Cardio-Oncology in Japan: The Rapidly Rising Sun.

JACC CardioOncol 2020 Dec 15;2(5):815-818. Epub 2020 Dec 15.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.jaccao.2020.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352098PMC
December 2020

Fasting Plasma Glucose and Incident Colorectal Cancer: Analysis of a Nationwide Epidemiological Database.

J Clin Endocrinol Metab 2021 Jun 25. Epub 2021 Jun 25.

Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.

Context: Although diabetes mellitus (DM) was reported to be associated with incident colorectal cancer (CRC), the detailed association between fasting plasma glucose (FPG) and incident CRC has not been fully understood.

Objective: We assessed whether hyperglycemia is associated with a higher risk for CRC.

Design: Analyses were conducted using the JMDC Claims Database [n = 1 441 311; median age (interquartile range), 46 (40-54) years; 56.6% men). None of the participants were taking antidiabetic medication or had a history of CRC, colorectal polyps, or inflammatory bowel disease. Participants were categorized as normal FPG (FPG level < 100 mg/dL; 1 125 647 individuals), normal-high FPG (FPG level = 100-109 mg/dL; 210 365 individuals), impaired fasting glucose (IFG; FPG level = 110-125 mg/dL; 74 836 individuals), and DM (FPG level ≥ 126 mg/dL; 30 463 individuals).

Results: Over a mean follow-up of 1137 ± 824 days, 5566 CRC events occurred. After multivariable adjustment, the hazard ratios for CRC events were 1.10 (95% CI 1.03-1.18) for normal-high FPG, 1.24 (95% CI 1.13-1.37) for IFG, and 1.36 (95% CI 1.19-1.55) for DM vs normal FPG. We confirmed this association in sensitivity analyses excluding those with a follow-up of< 365 days and obese participants.

Conclusion: The risk of CRC increased with elevated FPG category. FPG measurements would help to identify people at high-risk for future CRC.
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http://dx.doi.org/10.1210/clinem/dgab466DOI Listing
June 2021

Impact of the Geriatric Nutritional Risk Index in Patients Undergoing Transcatheter Aortic Valve Implantation.

Am J Cardiol 2021 Aug 6. Epub 2021 Aug 6.

Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California. Electronic address:

Several studies have shown that nutritional indexes are associated with cardiovascular events; however, limited studies have investigated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to evaluate the clinical impact of GNRI in patients undergoing TAVI. This single-center retrospective study analyzed consecutive patients treated with TAVI, stratified into groups according to their median baseline GNRI. The primary endpoint was 2-year all-cause mortality. In total, 968 patients with a mean age of 82.1 years and a median Society of Thoracic Surgeons (STS) score of 4.8% who underwent TAVI were included. The median GNRI was 103. Compared with the high-GNRI group (GNRI≥103, n = 451), the low-GNRI group (GNRI<103, n = 517) had higher STS scores and renal insufficiency rates. The 2-year all-cause mortality was significantly higher in the low-GNRI group than in the high-GNRI group (24.9% vs. 9.3%, p<0.001), despite no significant differences in procedural and clinical outcomes between the groups. On multivariable analysis, lower GNRI was independently associated with higher 2-year all-cause mortality (adjusted hazard ratio: 1.07; 95% confidence interval: 1.05-1.10; p<0.001). The GNRI retained its predictive value in subgroup analyses stratified by age (>75 vs. ≤75 years) and STS score (≥4 vs. <4). In conclusion, The GNRI is an important surrogate marker for predicting prognosis and mortality in patients undergoing TAVI.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.016DOI Listing
August 2021

Association of Body Mass Index with Ischemic and Hemorrhagic Stroke.

Nutrients 2021 Jul 9;13(7). Epub 2021 Jul 9.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Data on the association between body mass index (BMI) and stroke are scarce. We aimed to examine the association between BMI and incident stroke (ischemic or hemorrhagic) and to clarify the relationship between underweight, overweight, and obesity and stroke risk stratified by sex. We analyzed the JMDC Claims Database between January 2005 and April 2020 including 2,740,778 healthy individuals (Median (interquartile) age, 45 (38-53) years; 56.2% men; median (interquartile) BMI, 22.3 (20.2-24.8) kg/m). None of the participants had a history of cardiovascular disease. Each participant was categorized as underweight (BMI <18.5 kg/m), normal weight (BMI 18.5-24.9 kg/m), overweight (BMI 25.0-29.9 kg/m), or obese (BMI ≥ 30 kg/m). We investigated the association of BMI with incidence stroke in men and women using the Cox regression model. We used restricted cubic spline (RCS) functions to identify the association of BMI as a continuous parameter with incident stroke. The incidence (95% confidence interval) of total stroke, ischemic stroke, and hemorrhagic stroke was 32.5 (32.0-32.9), 28.1 (27.6-28.5), and 5.5 (5.3-5.7) per 10,000 person-years in men, whereas 25.7 (25.1-26.2), 22.5 (22.0-23.0), and 4.0 (3.8-4.2) per 10,000 person-years in women, respectively. Multivariable Cox regression analysis showed that overweight and obesity were associated with a higher incidence of total and ischemic stroke in both men and women. Underweight, overweight, and obesity were associated with a higher hemorrhagic stroke incidence in men, but not in women. Restricted cubic spline showed that the risk of ischemic stroke increased in a BMI dose-dependent manner in both men and women, whereas there was a U-shaped relationship between BMI and the hemorrhagic stroke risk in men. In conclusion, overweight and obesity were associated with a greater incidence of stroke and ischemic stroke in both men and women. Furthermore, underweight, overweight, and obesity were associated with a higher hemorrhagic stroke risk in men. Our results would help in the risk stratification of future stroke based on BMI.
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http://dx.doi.org/10.3390/nu13072343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308685PMC
July 2021

Automatic detection of vessel structure by deep learning using intravascular ultrasound images of the coronary arteries.

PLoS One 2021 5;16(8):e0255577. Epub 2021 Aug 5.

Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Intravascular ultrasound (IVUS) is a diagnostic modality used during percutaneous coronary intervention. However, specialist skills are required to interpret IVUS images. To address this issue, we developed a new artificial intelligence (AI) program that categorizes vessel components, including calcification and stents, seen in IVUS images of complex lesions. When developing our AI using U-Net, IVUS images were taken from patients with angina pectoris and were manually segmented into the following categories: lumen area, medial plus plaque area, calcification, and stent. To evaluate our AI's performance, we calculated the classification accuracy of vessel components in IVUS images of vessels with clinically significantly narrowed lumina (< 4 mm2) and those with severe calcification. Additionally, we assessed the correlation between lumen areas in manually-labeled ground truth images and those in AI-predicted images, the mean intersection over union (IoU) of a test set, and the recall score for detecting stent struts in each IVUS image in which a stent was present in the test set. Among 3738 labeled images, 323 were randomly selected for use as a test set. The remaining 3415 images were used for training. The classification accuracies for vessels with significantly narrowed lumina and those with severe calcification were 0.97 and 0.98, respectively. Additionally, there was a significant correlation in the lumen area between the ground truth images and the predicted images (ρ = 0.97, R2 = 0.97, p < 0.001). However, the mean IoU of the test set was 0.66 and the recall score for detecting stent struts was 0.64. Our AI program accurately classified vessels requiring treatment and vessel components, except for stents in IVUS images of complex lesions. AI may be a powerful tool for assisting in the interpretation of IVUS imaging and could promote the popularization of IVUS-guided percutaneous coronary intervention in a clinical setting.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255577PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341597PMC
August 2021

Combined evaluation of right ventricular function using echocardiography in non-ischaemic dilated cardiomyopathy.

ESC Heart Fail 2021 Aug 4. Epub 2021 Aug 4.

Department of Cardiovascular Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Aims: Although comprehensive assessment of right ventricular (RV) function using multiple echocardiographic parameters is recommended for management of patients with non-ischaemic dilated cardiomyopathy (DCM), it is unclear which RV parameters to combine. Additionally, normalization of RV parameters by estimated pulmonary artery systolic pressure (PASP), in consideration of RV-pulmonary artery coupling, may be clinically significant. The aim of our study was to elucidate the best combination of echocardiographic RV functional parameters, with or without indexing for PASP, to predict outcome in patients with heart failure with reduced ejection fraction secondary to DCM.

Methods And Results: We retrospectively analysed 109 DCM patients with left ventricular ejection fraction <40%. RV size was assessed by RV end-diastolic area (RVEDA) and RV end-systolic area (RVESA) from RV-focused apical four-chamber view. RV function was assessed by fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) and by RV longitudinal strain (RVLS) using two-dimensional speckle-tracking echocardiography. All functional parameters were also indexed for estimated PASP. Cox analyses were used to evaluate the association of RV morphology and functional parameters with 1 year outcome (composite of left ventricular assist device implantation and all-cause death). Area under the curve was used to compare prognostic values. Mean age was 44 ± 14 years, and 76 (69.7%) were men. Mean left ventricular ejection fraction was 21.9%, median RVEDA was 22.1 cm , FAC was 27.0%, TAPSE was 15.0 mm, and RVLS was -12.5%. Forty-one (37.6%) patients experienced the primary outcome. Multivariate Cox analysis revealed that RVEDA, RVESA, FAC, TAPSE, RVLS, FAC/PASP, and RVLS/PASP were independent predictors for primary outcome (all P < 0.05). However, normalization with PASP did not improve area under the curve for any RV functional parameters. When we evaluate hazard ratios according to the combination of two echocardiographic parameters of RV function, patients with impairment of both FAC (<27%) and RVLS (>-8.6%) had significantly higher hazard ratio than those with either impairment alone (11.3 vs. 3.4, P < 0.001); the other combinations did not improve prognostic value.

Conclusions: Normalizing echocardiographic RV parameters for PASP did not improve the prognostic values for our population. Meanwhile, combined evaluation of FAC and RVLS improved risk stratification in patients with heart failure with reduced ejection fraction secondary to DCM.
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http://dx.doi.org/10.1002/ehf2.13519DOI Listing
August 2021

Possible Gender Difference in the Association Between Abdominal Obesity, Chronic Inflammation, and Preclinical Atherosclerosis in the General Population.

Int Heart J 2021 ;62(4):837-842

Department of Cardiovascular Medicine, School of Medicine, The University of Tokyo.

Chronic inflammation due to abdominal obesity plays a major role in the development of cardiovascular disease (CVD). Gender differences are well characterized in the development of CVD; however, in the association among abdominal obesity, chronic inflammation, and preclinical atherosclerosis, gender differences in the general population remain to be clarified. We retrospectively analyzed 1,163 subjects who underwent voluntary health checkups at our institute. We defined carotid artery plaque formation as carotid intima-media thickness ≥ 1.1 mm. Multiple regression analysis showed that waist circumference was a major independent predictor of increase in serum C-reactive protein (CRP) level in both men and women. Serum CRP level was significantly increased in men with carotid artery plaque formation, but not in women. Multivariable logistic regression analysis demonstrated that serum CRP level, as well as age and hypertension, was independently associated with carotid artery plaque formation only in men. This result may suggest a potential of gender-specific difference in the association between serum CRP level and the prevalence of carotid artery plaque formation. Further investigations are required to confirm our results and to clarify the underlying mechanism.
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http://dx.doi.org/10.1536/ihj.20-654DOI Listing
August 2021

Clinical Impact of Copy Number Variation on the Genetic Diagnosis of Syndromic Aortopathies.

Circ Genom Precis Med 2021 Aug 30;14(4):e003458. Epub 2021 Jul 30.

Department of Cardiovascular Medicine (N.T., H. Yagi, H.M., T.K., I.K.), University of Tokyo Hospital, Japan.

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http://dx.doi.org/10.1161/CIRCGEN.121.003458DOI Listing
August 2021

Single-Cardiomyocyte RNA Sequencing to Dissect the Molecular Pathophysiology of the Heart.

Methods Mol Biol 2021 ;2320:183-192

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Heart failure is caused by a complicated pathogenic process and has a poor prognosis. Quality of life is often impaired due to repeated hospitalization. Integrative analysis of the morphological, physiological, and molecular profiles of cardiomyocytes, which are responsible mainly for heart contraction, may lead to a deeper understanding of the pathogenesis of heart failure. However, unlike other types of cells, cardiomyocytes are relatively large, vulnerable to stress, and difficult to use for single-cell analysis. With some ingenuity, we have established a single-cardiomyocyte analysis pipeline. Here, we describe the procedure for single-cell RNA sequencing of adult mouse cardiomyocytes from isolation to analysis.
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http://dx.doi.org/10.1007/978-1-0716-1484-6_18DOI Listing
August 2021

Risk Factors and Lifestyles in the Development of Atrial Fibrillation Among Individuals Aged 20-39 Years.

Am J Cardiol 2021 09 19;155:40-44. Epub 2021 Jul 19.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Epidemiological evidence on the relationship of modifiable risk factors and lifestyles with incident atrial fibrillation (AF) in young adults remains insufficient. We aimed to identify the determinants of AF among young adults using a nationwide epidemiological database. Medical records of 286,876 individuals (20-39 years) without prior history of cardiovascular disease were extracted from the JMDC Claims Database. We analyzed the association of modifiable risk factors with the incidence of AF. The median (interquartile range) age was 34 (29-37) years, and 54.4% were men. After a mean follow-up of 1,017 ± 836 days, 267 individuals (0.1%) developed AF. Multivariable Cox regression analysis demonstrated that high waist circumference, hypertension, cigarette smoking, and poor sleep quality as well as age and sex were associated with increased incidence of AF. Kaplan-Meier curves showed that number of modifiable components including high waist circumference, hypertension, cigarette smoking, and poor sleep quality clearly stratified the risk of AF development (Log rank test, p < 0.001). Age- and sex-adjusted Cox regression analyses showed individuals with one (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.13-2.18), two (HR 2.03, 95% CI 1.40-2.95), three (HR 3.48, 95% CI 2.19-5.54), and four (HR 10.78, 95% CI 5.26-22.11) components were associated with an increased incidence of AF compared with individuals with no components. In conclusion, high waist circumference, hypertension, cigarette smoking, and poor sleep quality were associated with the development of AF among young adults, suggesting the importance of maintaining these modifiable factors for the primordial prevention of AF in young adults.
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http://dx.doi.org/10.1016/j.amjcard.2021.06.010DOI Listing
September 2021

Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression.

J Clin Invest 2021 Aug;131(16)

Division of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan.

The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.
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http://dx.doi.org/10.1172/JCI145693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363285PMC
August 2021

Deep Learning Algorithm to Detect Cardiac Sarcoidosis From Echocardiographic Movies.

Circ J 2021 Jun 26. Epub 2021 Jun 26.

Department of Cardiovascular Medicine, The University of Tokyo Hospital.

Background: Because the early diagnosis of subclinical cardiac sarcoidosis (CS) remains difficult, we developed a deep learning algorithm to distinguish CS patients from healthy subjects using echocardiographic movies.Methods and Results:Among the patients who underwent echocardiography from January 2015 to December 2019, we chose 151 echocardiographic movies from 50 CS patients and 151 from 149 healthy subjects. We trained two 3D convolutional neural networks (3D-CNN) to identify CS patients using a dataset of 212 echocardiographic movies with and without a transfer learning method (Pretrained algorithm and Non-pretrained algorithm). On an independent set of 41 echocardiographic movies, the area under the receiver-operating characteristic curve (AUC) of the Pretrained algorithm was greater than that of Non-pretrained algorithm (0.842, 95% confidence interval (CI): 0.722-0.962 vs. 0.724, 95% CI: 0.566-0.882, P=0.253). The AUC from the interpretation of the same set of 41 echocardiographic movies by 5 cardiologists was not significantly different from that of the Pretrained algorithm (0.855, 95% CI: 0.735-0.975 vs. 0.842, 95% CI: 0.722-0.962, P=0.885). A sensitivity map demonstrated that the Pretrained algorithm focused on the area of the mitral valve.

Conclusions: A 3D-CNN with a transfer learning method may be a promising tool for detecting CS using an echocardiographic movie.
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http://dx.doi.org/10.1253/circj.CJ-21-0265DOI Listing
June 2021

Fasting Plasma Glucose and Incident Colorectal Cancer: Analysis of a Nationwide Epidemiological Database Fasting Plasma Glucose and Colorectal Cancer.

J Clin Endocrinol Metab 2021 Jun 25. Epub 2021 Jun 25.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Context: Although diabetes mellitus (DM) was reported to be associated with incident colorectal cancer (CRC), the detailed association between fasting plasma glucose (FPG) and incident CRC has not been fully understood.

Objective: We assessed whether hyperglycemia is associated with a higher risk for CRC.

Design: Analyses were conducted using the JMDC Claims Database (n=1,441,311; median age [IQR], 46 [40-54] years; 56.6% men). None of the participants were taking antidiabetic medication or had a history of CRC, colorectal polyps, or inflammatory bowel disease. Participants were categorized as normal FPG, FPG level<100 mg/dL (1,125,647 individuals); normal-high FPG, FPG level=100-109 mg/dL (210,365 individuals); impaired fasting glucose (IFG), FPG level=110-125 mg/dL (74,836 individuals); and DM, FPG level≥126 mg/dL (30,463 individuals).

Results: Over a mean follow-up of 1,137±824 days, 5,566 CRC events occurred. After multivariable adjustment, the hazard ratios for CRC events were 1.10 (95% CI,1.03-1.18) for normal-high FPG, 1.24 (95% CI, 1.13-1.37) for IFG, and 1.36 (95% CI, 1.19-1.55) for DM vs. normal FPG. We confirmed this association in sensitivity analyses excluding those with a follow-up of< 365 days, and or with obese participants.

Conclusion: The risk of CRC increased with elevated FPG category. FPG measurements would help identifying people at high-risk for future CRC.
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http://dx.doi.org/10.1210/clinem/dgab466DOI Listing
June 2021

Pseudo-elevation of conduction system pacing threshold through parallel connection of an intracardiac electrogram recording system.

J Cardiovasc Electrophysiol 2021 Aug 1;32(8):2329-2332. Epub 2021 Jul 1.

Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Parallel connection of an electrophysiology recording system (EP system) to equipment for conduction system pacing (CSP) has been widely used for fine monitoring of intracardiac electrograms and pacing evaluation. We experienced a case showing unexpected pacing threshold exacerbation under specific conditions when the EP system was connected in parallel. We evaluated the underlying mechanism using an ex vivo model. An ex vivo pacing and intracardiac electrogram monitoring model was generated using an oscilloscope, pacing system analyzer (PSA), EP system, and simulated heart. The discrepancy between expected output at the PSA and the actual measured output value at the simulated heart was measured under various conditions and using various combinations of pacing equipment. Parallel connection of the EP system was associated with reduced electrical output from the PSA as recorded at the simulated heart. The unexpected adverse effects were particularly noticeable when using an RMC-5000 EP system with the pacing function on. The trouble is completely resolved by simply turning off the pacing function of the system. There is a possibility that the EP system might increase the pacing threshold in CSP when the PSA and EP system is are deployed in parallel. The issue may provoke pseudo failure of CSP due to the high pacing threshold. When the RMC-5000 is used for conduction system pacing in parallel with a PSA for the pacing test, the pacing function of RMC-5000 should be turned off.
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http://dx.doi.org/10.1111/jce.15129DOI Listing
August 2021

Relation of Serum Uric Acid and Cardiovascular Events in Young Adults Aged 20-49 Years.

Am J Cardiol 2021 08 14;152:150-157. Epub 2021 Jun 14.

The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Serum uric acid (SUA) was reported to be associated with incident cardiovascular disease (CVD). However, the relationship between SUA and CVD among young adults has not been clarified yet. In this study, we aimed to identify the association of medication naïve SUA with incident CVD including myocardial infarction (MI), stroke, heart failure (HF) and atrial fibrillation (AF) using a nationwide epidemiological database. We analyzed 353,613 participants aged 20-49 years, who were not taking UA lowering medications, and had no prevalent history of cardiovascular disease (CVD) using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018. Median [interquartile range] age was 40 [34-44] years, and 46.9% were men. Over a mean follow-up of 1,176±876 days, 391 (0.1%) incident MI, 1,308 (0.4%) incident stroke, 3,374 (1.0%) incident HF, and 684 (0.2%) incident AF events occurred. Kaplan-Meier curves and the log-rank test showed that there was a significant difference in incident MI, stroke, HF, and AF among the groups based on SUA tertile (all log-rank p< 0.001). Multivariable Cox regression analysis showed that the upper tertile of SUA (SUA ≥ 5.7 mg/dL) was associated with higher incidence of MI (HR 1.45, 95% CI 1.00-2.10), HF (HR 1.13, 95% CI 1.01-1.28), and AF (HR 1.35, 95% CI 1.02-1.78) compared with the first tertile of SUA (SUA < 4.4 mg/dL). SUA as continuous variable was independently associated with incident MI (HR 1.10, 95% CI 1.00-1.20), stroke (HR 1.06, 95% CI 1.00-1.11), HF (HR 1.07, 95% CI 1.03-1.10), and AF (HR 1.11, 95% CI 1.04-1.19). SUA ≥ 7.0 mg/dL was independently associated with incident HF (HR 1.24, 95% CI 1.12-1.38). In conclusion, higher SUA was associated with increased incidence of CVD events in individuals aged< 50 years, suggesting the potential significance of the optimal UA control for the primary CVD prevention even in young adults.
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http://dx.doi.org/10.1016/j.amjcard.2021.05.007DOI Listing
August 2021
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