Publications by authors named "Hiroyuki Tsutsui"

501 Publications

Efficacy of thromboelastography in the management of anticoagulation for veno-venous extracorporeal membrane oxygenation in a coronavirus disease 2019 patient: A case report.

Medicine (Baltimore) 2021 Jun;100(23):e26313

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

Rationale: In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO.

Patient Concerns: A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome.

Diagnoses: He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent.

Interventions: Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min).

Outcomes: Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient's respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased.

Lessons: TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.
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http://dx.doi.org/10.1097/MD.0000000000026313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202565PMC
June 2021

Nanoparticle-Mediated Simultaneous Targeting of Mitochondrial Injury and Inflammation Attenuates Myocardial Ischemia-Reperfusion Injury.

J Am Heart Assoc 2021 Jun 29;10(12):e019521. Epub 2021 May 29.

Department of Cardiovascular Research Development, and Translational Medicine Center for Disruptive Cardiovascular Innovation Kyushu University Fukuoka Japan.

Background The opening of mitochondrial permeability transition pore and inflammation cooperatively progress myocardial ischemia-reperfusion (IR) injury, which hampers therapeutic effects of primary reperfusion therapy for acute myocardial infarction. We examined the therapeutic effects of nanoparticle-mediated medicine that simultaneously targets mitochondrial permeability transition pore and inflammation during IR injury. Methods and Results We used mice lacking cyclophilin D (CypD, a key molecule for mitochondrial permeability transition pore opening) and C-C chemokine receptor 2 and found that CypD contributes to the progression of myocardial IR injury at early time point (30-45 minutes) after reperfusion, whereas C-C chemokine receptor 2 contributes to IR injury at later time point (45-60 minutes) after reperfusion. Double deficiency of CypD and C-C chemokine receptor 2 enhanced cardioprotection compared with single deficiency regardless of the durations of ischemia. Deletion of C-C chemokine receptor 2, but not deletion of CypD, decreased the recruitment of Ly-6C monocytes after myocardial IR injury. In CypD-knockout mice, administration of interleukin-1β blocking antibody reduced the recruitment of these monocytes. Combined administration of polymeric nanoparticles composed of poly-lactic/glycolic acid and encapsulating nanoparticles containing cyclosporine A or pitavastatin, which inhibit mitochondrial permeability transition pore opening and monocyte-mediated inflammation, respectively, augmented the cardioprotection as compared with single administration of nanoparticles containing cyclosporine A or pitavastatin after myocardial IR injury. Conclusions Nanoparticle-mediated simultaneous targeting of mitochondrial injury and inflammation could be a novel therapeutic strategy for the treatment of myocardial IR injury.
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http://dx.doi.org/10.1161/JAHA.120.019521DOI Listing
June 2021

Beta-Blocker Use Is Associated With Prevention of Left Ventricular Remodeling in Recovered Dilated Cardiomyopathy.

J Am Heart Assoc 2021 Jun 31;10(12):e019240. Epub 2021 May 31.

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

Background Withdrawal of optimal medical therapy has been reported to relapse cardiac dysfunction in patients with dilated cardiomyopathy (DCM) whose cardiac function had improved. However, it is unknown whether beta-blockers can prevent deterioration of cardiac function in those patients. We examined the effect of beta-blockers on left ventricular ejection fraction (LVEF) in recovered DCM. Methods and Results We analyzed the clinical personal record of DCM, a national database of the Japanese Ministry of Health, Labor and Welfare, between 2003 and 2014. Recovered DCM was defined as a previously documented LVEF <40% and a current LVEF ≥40%. Patients with recovered DCM were divided into 2 groups according to the use of beta-blockers. A one-to-one propensity case-matched analysis was used. The primary outcome was defined as a decrease in LVEF >10% at 2 years of follow-up. Of 5370 eligible patients, 4104 received beta-blockers. Propensity score matching yielded 1087 pairs. Mean age was 61.9 years, and 1619 (74.5%) were men. Mean LVEF was 49.3±8.2%, and median B-type natriuretic peptide was 46.6 (interquartile range, 18.0-118.1) pg/mL. The primary outcome was observed less frequently in the beta-blocker group than in the no-beta-blocker group (19.6% versus 24.0%; odds ratio [OR], 0.77; 95% CI, 0.63-0.95; =0.013). Subgroup analysis demonstrated that female patients (women: OR, 0.54; 95% CI, 0.36-0.81; men: OR, 0.88; 95% CI, 0.69-1.12; for interaction=0.040) were benefited by beta-blockers. Conclusions Beta-blocker use could prevent deterioration of left ventricular systolic function in patients with recovered DCM.
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http://dx.doi.org/10.1161/JAHA.120.019240DOI Listing
June 2021

Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Attenuates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm in Obese Mice.

Front Cardiovasc Med 2021 10;8:659418. Epub 2021 May 10.

Department of Cardiovascular Medicine, Kyushu University Graduate School of Medicine, Fukuoka, Japan.

The infiltration and activation of macrophages as well as lymphocytes within the aorta contribute to the pathogenesis of abdominal aortic aneurysm (AAA). Invariant natural killer T (iNKT) cells are unique subset of T lymphocytes and have a crucial role in atherogenesis. However, it remains unclear whether iNKT cells also impact on the development of AAA. mice were administered angiotensin II (AngII, 1,000 ng/kg/min) or phosphate-buffered saline (PBS) by osmotic minipumps for 4 weeks and further divided into 2 groups; α-galactosylceramide (αGC; PBS-αGC; = 5 and AngII-αGC; = 12), which specifically activates iNKT cells, and PBS (PBS-PBS; = 10, and AngII-PBS; = 6). Maximal abdominal aortic diameter was comparable between PBS-PBS and PBS-αGC, and was significantly greater in AngII-PBS than in PBS-PBS. This increase was significantly attenuated in AngII-αGC without affecting blood pressure. αGC significantly enhanced iNKT cell infiltration compared to PBS-PBS. The ratio of F4/80-positive macrophages or CD3-positive T lymphocytes area to the lesion area was significantly higher in AngII-PBS than in PBS-PBS, and was significantly decreased in AngII-αGC. Gene expression of M2-macrophage specific markers, arginase-1 and resistin-like molecule alpha, was significantly greater in aortic tissues from AngII-αGC compared to AngII-PBS 1 week after AngII administration, and this increase was diminished at 4 weeks. Activation of iNKT cells by αGC can attenuate AngII-mediated AAA in mice via inducing anti-inflammatory M2 polarized state. Activation of iNKT cells by the bioactive lipid αGC may be a novel therapeutic target against the development of AAA.
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http://dx.doi.org/10.3389/fcvm.2021.659418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141584PMC
May 2021

HFA/HFSA/JHFS Position Statement on Endomyocardial Biopsy.

J Card Fail 2021 Apr 27. Epub 2021 Apr 27.

Cleveland Clinic, Cleveland OH, USA.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: 1) an overview of the practical approach to EMB, 2) an update on indications for EMB, 3) a revised plan for HTx rejection surveillance, 4) the impact of multimodality imaging on EMB, and 5) the current clinical practice in the worldwide use of EMB.
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http://dx.doi.org/10.1016/j.cardfail.2021.04.010DOI Listing
April 2021

Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy.

Eur J Heart Fail 2021 May 19. Epub 2021 May 19.

Cleveland Clinic, Cleveland, OH, USA.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.
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http://dx.doi.org/10.1002/ejhf.2190DOI Listing
May 2021

Background characteristics and anticoagulant usage patterns of elderly non-valvular atrial fibrillation patients in the ANAFIE registry: a prospective, multicentre, observational cohort study in Japan.

BMJ Open 2021 03 8;11(3):e044501. Epub 2021 Mar 8.

Saiseikai Toyama Hospital, Toyama, Japan.

Objective: To explore anticoagulant usage patterns stratified by stroke and bleeding risk in elderly patients with non-valvular atrial fibrillation (NVAF).

Design: Prospective, multicentre, observational cohort study.

Setting: The real-world All Nippon AF In the Elderly (ANAFIE) registry.

Participants: Japanese patients aged ≥75 years with NVAF (n=32 726).

Outcome Measures: The distribution of stroke and bleeding risk scores, and the selection of anticoagulant regimen for patients at high stroke and bleeding risk.

Results: Overall, 18 185 (55.6%) patients had a high risk of stroke (CHADS score ≥3). Of these, 12 561 (38.4% of the total ANAFIE population) had a low bleeding risk (HAS-BLED ≤2) and 5624 (17.2%) had a high bleeding risk (HAS-BLED ≥3). Significant differences were noted between the high versus low bleeding risk groups in sex, height, weight, systolic blood pressure and rates of abnormality of lipid metabolism, gastrointestinal disease, cerebrovascular disorders, chronic kidney disease, angina pectoris, respiratory disease, primary malignant tumour, dementia and fall history within the past year (all p<0.0001). Patients with high stroke and bleeding risks had a lower anticoagulant usage rate versus the low bleeding risk group, and 8.7% and 5.8%, respectively, were not receiving any anticoagulant (p<0.0001). Patients in the high bleeding risk group had a higher usage of warfarin versus the low bleeding risk group (p<0.0001); more patients (14.0%) in the high bleeding risk group receiving warfarin had time in the therapeutic range <40%, versus those in the low bleeding risk group (11.6%, p=0.0146). Direct-acting oral anticoagulants (DOACs) were used less in the high bleeding risk group, without notable differences in the DOAC dose distribution between the two groups.

Conclusions: In elderly NVAF patients at high stroke risk, significant demographic and clinical differences were observed according to bleeding risk. Administration of low-dose DOACs was frequent, but the dose distribution was unaffected by bleeding risk.

Trial Registration Number: UMIN000024006 (http://www.umin.ac.jp/).
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http://dx.doi.org/10.1136/bmjopen-2020-044501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942257PMC
March 2021

Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability.

J Hypertens 2021 Jul;39(7):1435-1443

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

Background: Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, the evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. We investigated the effectiveness of intensive versus standard statin therapy in the primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability.

Methods: The standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy study was the first trial comparing statin intensive therapy targeting low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and standard therapy targeting LDL-C ≥100 to <120 mg/dl in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within the initial 6 months.

Results: In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45-0.90) and 1.21 (95% CI 0.82-1.80) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (P = 0.018). The analysis using ARV of SBP showed similar results.

Conclusion: Statin intensive therapy targeting LDL-C <70 mg/dl had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit-to-visit SBP variability.
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http://dx.doi.org/10.1097/HJH.0000000000002823DOI Listing
July 2021

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis.

Nat Commun 2021 05 13;12(1):2783. Epub 2021 May 13.

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Dysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.
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http://dx.doi.org/10.1038/s41467-021-23050-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119956PMC
May 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 Apr 15. 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 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
April 2021

Bigeminal potentials in the pulmonary vein indicate arrhythmogenic trigger of atrial fibrillation.

J Arrhythm 2021 Apr 19;37(2):331-337. Epub 2021 Jan 19.

Department of Cardiovascular Medicine Kyushu University Hospital Fukuoka Japan.

Background: The pulmonary veins (PVs) have unique electrophysiological properties triggering and maintaining atrial fibrillation (AF). Bigeminal PV electrical activity (PV bigeminy) during sinus rhythm has been reported; however, its mechanisms and clinical implication remain unclear. We hypothesized that PV bigeminy indicates arrhythmogenic activities and influences clinical outcome.

Methods And Results: We retrospectively analyzed electrophysiological studies in 465 patients with AF who underwent first session PV isolation (PVI). PV bigeminy was observed in 30 PVs of 23 patients (4.9% of patients). PV bigeminy was observed in left inferior PV (LIPV) in 15 patients, which was the most prevalent, followed by left superior in seven and right superior in seven and right inferior in one. In response to atrial extra stimulus, the second PV potentials (PV2) showed decremental conduction properties, suggesting reentrant mechanisms involved (n = 5). Interestingly, AF was initiated from the 23 PVs with bigeminy in 21 patients (76.7% of 30 PVs with bigeminy), spontaneously or in response to drugs, which was significantly more prevalent from the AF initiation rate from each PV in the control 442 patients (182 firings in 1290 PVs, 14.1%,  < .0001). PVI-based ablation was completed in the 23 patients with PV bigeminy and no recurrence was observed during 1-year follow-up, whereas four patients needed second sessions.

Conclusions: PV bigeminy is relatively rare but a unique electrophysiological finding in AF patients, suggesting reentrant substrate within the PV and/or surrounding tissue. PV bigeminy is a strong indicator of arrhythmogenic vein triggering AF, and ensures an excellent clinical outcome after PVI.
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http://dx.doi.org/10.1002/joa3.12462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021992PMC
April 2021

Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study.

Environ Health Prev Med 2021 Apr 12;26(1):47. Epub 2021 Apr 12.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population.

Methods: A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model.

Results: The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R] = 0.72): urinary concentrations of 20, 27, and 43 pg/mL were equivalent to serum concentrations of 55, 125, and 300 pg/mL, respectively. During the follow-up period, 170 subjects developed CVD. The age- and sex-adjusted risk of CVD increased significantly with higher urinary NT-proBNP levels (P for trend < 0.001). This association remained significant after adjustment for traditional cardiovascular risk factors (P for trend = 0.009). The multivariable-adjusted risk of developing CVD almost doubled in subjects with urinary NT-proBNP of ≥ 43 pg/mL as compared to those with urinary NT-proBNP of ≤ 19 pg/mL (HR 2.07, 95% CI 1.20-3.56).

Conclusions: The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.
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http://dx.doi.org/10.1186/s12199-021-00970-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042718PMC
April 2021

Two-year outcomes of more than 30 000 elderly patients with atrial fibrillation: results from the All Nippon AF In the Elderly (ANAFIE) Registry.

Eur Heart J Qual Care Clin Outcomes 2021 Apr 2. Epub 2021 Apr 2.

Data Intelligence Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.

Aims: To clarify the real-world clinical status and prognosis of elderly and very elderly non-valvular atrial fibrillation (NVAF) patients, more than 30 000 elderly patients with NVAF aged ≥75 years were enrolled in the ANAFIE Registry.

Methods And Results: This multicentre, prospective, observational study followed elderly NVAF patients in Japan for ∼2 years. Among 32 275 patients (mean age 81.5 years; men, 57.3%; mean CHA2DS2-VASc score 4.5), 2445 (7.6%) were not receiving oral anticoagulants (OACs) and 29 830 (92.4%) were given OACs. Of these, 21 585 (66.9%) were receiving direct OACs (DOACs) and 8233 (25.5%), warfarin (mean time in therapeutic range: ∼75%). In total, the 2-year incidence rate was 3.01% for stroke/systemic embolic events (SEE); 2.00%, major bleeding; and 6.95%, all-cause death. As compared with the warfarin group, the DOAC group had a lower hazard ratio (HR) for stroke/SEE, major bleeding, and all-cause death after adjusting for confounders. The group without OACs had a higher HR for stroke/SEE and all-cause death, with a lower HR for major bleeding. History of falls within 1 year at enrolment and of catheter ablation were positive and negative independent risk factors, respectively, for stroke/SEE, major bleeding and all-cause death.

Conclusion: In Japan, a large proportion of elderly and very elderly NVAF patients were receiving DOACs, which was significantly associated with lower rate of stroke/SEE, major bleeding, and all-cause death vs well-controlled warfarin. History of falls and of catheter ablation were independently associated with stroke/SEE, major bleeding, and all-cause death.
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http://dx.doi.org/10.1093/ehjqcco/qcab025DOI Listing
April 2021

Usefulness of F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Infective Endocarditis in Patients With Adult Congenital Heart Disease.

Circ J 2021 Apr 1. Epub 2021 Apr 1.

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

Background: Infective endocarditis (IE) in patients with adult congenital heart disease (ACHD) remains a diagnostic challenge due to difficulties in detecting endocardial lesions by echocardiography. F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) has shown good diagnostic performance in prosthetic valve IE. This study aimed to assess its additional diagnostic value in ACHD-associated IE and to characterize its advantages.Methods and Results:Overall, 22 patients with ACHD and clinical suspicion of IE were retrospectively studied. F-FDG PET/CT was performed in addition to conventional assessment based on the modified Duke criteria. The final IE diagnosis was determined by an expert team during a 3-month clinical course, resulting in 18 patients diagnosed with IE. Seven patients (39%) were diagnosed with definite IE only by initial echocardiography. An F-FDG PET/CT assessment revealed endocardial involvement in the other 9 patients, resulting in the diagnosis of definite IE in 16 in total (88%). Right-sided endocardial lesions were more common (n=12, 67%) but rarely identified by echocardiography, whereas F-FDG PET/CT revealed right-sided lesions in 9 patients. A negative F-FDG PET/CT (n=7, 39%) assessment was associated with a native valve IE (71% vs. 0%). In 4 patients who were identified with not-IE, neither echocardiography nor F-FDG PET/CT detected any suspicious cardiac involvement.

Conclusions: In the diagnosis of ACHD-associated IE, characterized by right-sided IE, F-FDG PET/CT assessment should be useful.
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http://dx.doi.org/10.1253/circj.CJ-20-1067DOI Listing
April 2021

Chronic Inhibition of Toll-Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats.

J Am Heart Assoc 2021 Apr 31;10(7):e019247. Epub 2021 Mar 31.

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

Background Recent accumulating evidence suggests that toll-like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases. However, its role in pulmonary hypertension remains uncertain. We hypothesized that TLR9 is involved in the development of pulmonary hypertension. Methods and Results A rat model of monocrotaline-induced pulmonary hypertension was used to investigate the effects of TLR9 on hemodynamic parameters, vascular remodeling, and survival. Monocrotaline-exposed rats significantly showed increases in plasma levels of mitochondrial DNA markers, which are recognized by TLR9, TLR9 activation in the lung, and mRNA level in the lung on day 14 after monocrotaline injection. Meanwhile, monocrotaline-exposed rats showed elevated right ventricular systolic pressure, total pulmonary vascular resistance index and vascular remodeling, together with macrophage accumulation on day 21. In the preventive protocol, administration (days -3 to 21 after monocrotaline injection) of selective (E6446) or nonselective TLR9 inhibitor (chloroquine) significantly ameliorated the elevations of right ventricular systolic pressure and total pulmonary vascular resistance index as well as vascular remodeling and macrophage accumulation on day 21. These inhibitors also significantly reduced NF-κB activation and mRNA levels to a similar extent. In the short-term reversal protocol, E646 treatment (days 14-17 after monocrotaline injection) almost normalized NF-κB activation and mRNA level, and reduced macrophage accumulation. In the prolonged reversal protocol, E6446 treatment (days 14-24 after monocrotaline injection) reversed total pulmonary vascular resistance index and vascular remodeling, and improved survival in monocrotaline-exposed rats. Conclusions TLR9 is involved in the development of pulmonary hypertension concomitant via activation of the NF-κB‒IL-6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.
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http://dx.doi.org/10.1161/JAHA.120.019247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174358PMC
April 2021

Clinical Characteristics and Contemporary Management of Patients With Cardiomyopathies in Japan - Report From a National Registry of Clinical Personal Records.

Circ Rep 2021 Feb 11;3(3):142-152. Epub 2021 Feb 11.

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

The clinical features of patients with cardiomyopathy, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or restrictive cardiomyopathy (RCM), have not been recently elucidated in Japan. We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM from 2003 to 2014 and in HCM and RCM from 2009 to 2014 from the national registry of clinical personal records organized by the Japanese Ministry of Health, Labour and Welfare. In all, 44,136 patients were included in this registry: 40,537 with DCM, 3,553 with HCM, and 46 with RCM. The median age at diagnosis was older for DCM and HCM than RCM (54 and 55 vs. 42 years, respectively). Male patients accounted for 74.6%, 58.7%, and 60.9% of the DCM, HCM, and RCM groups, respectively. NYHA functional Class III-IV was found in 26.9%, 11.3%, and 58.1% of patients in the DCM, HCM, and RCM groups, respectively. In the DCM group, the rates of β-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription were 69% and 76%, respectively. In regional subgroup analysis, the median age at diagnosis of DCM and HCM was younger in the Kanto region. A family history of HCM was less frequent in the Hokkaido/Tohoku region. The national registry of clinical personal records of cardiomyopathy could provide important information regarding the demographics, clinical characteristics, and management of cardiomyopathy throughout Japan.
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http://dx.doi.org/10.1253/circrep.CR-21-0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956877PMC
February 2021

Cardiology Department Practices in the First Wave of the Coronavirus Disease Pandemic - A Nationwide Survey in Japan by the Japanese Circulation Society.

Circ Rep 2021 Feb 5;3(3):137-141. Epub 2021 Feb 5.

Department of Cardiovascular Medicine, Saga University Saga Japan.

From the early phase of the Coronavirus disease-2019 (COVID-19) pandemic, cardiologists have paid attention not only to COVID-19-associated cardiovascular sequelae, but also to treatment strategies for rescheduling non-urgent procedures. The chief objective of this study was to explore confirmed COVID-19 cardiology case experiences and departmental policies, and their regional heterogeneity in Japan. We performed a retrospective analysis of a nationwide survey performed by the Japanese Circulation Society on April 13, 2020. The questionnaire included cardiology department experience with confirmed COVID-19 cases and restriction policies, and was sent to 1,360 certified cardiology training hospitals. Descriptive analysis and spatial autocorrelation analysis of each response were performed to reveal the heterogeneity of departmental policies. The response rate was 56.8% (773 replies). Only 16% of all responding hospitals experienced a COVID-19 cardiology case. High-risk procedures were restricted in more than one-fifth of hospitals, including transesophageal echocardiography (34.9%) and scheduled catheterization (39.5%). The presence of a cardiologist in the COVID-19 team, the number of board-certified cardiologists, any medical resource shortage and a state of emergency were positively correlated with any type of restriction. We found both low clinical case experiences with COVID-19 and restrictions of cardiovascular procedures during the first COVID-19 wave in Japan. Restrictions arising as a result of COVID-19 were affected by hospital- and country-level variables, such as a state of emergency.
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http://dx.doi.org/10.1253/circrep.CR-21-0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956880PMC
February 2021

Efficacy and Safety of Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction - Results From the PARALLEL-HF Study.

Circ J 2021 Apr 16;85(5):584-594. Epub 2021 Mar 16.

Novartis Pharmaceutical Corporation.

Background: In the Prospective Comparison of angiotensin receptor neprilysin inhibitor (ARNI) With ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study, treatment with sacubitril/valsartan reduced the primary outcome of cardiovascular (CV) death and heart failure (HF) hospitalization compared with enalapril in patients with chronic HF and reduced ejection fraction (HFrEF). A prospective randomized trial was conducted to assess the efficacy and safety of sacubitril/valsartan in Japanese HFrEF patients.Methods and Results:In the Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients (PARALLEL-HF) study, 225 Japanese HFrEF patients (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF] ≤35%) were randomized (1 : 1) to receive sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Over a median follow up of 33.9 months, no significant between-group difference was observed for the primary composite outcome of CV death and HF hospitalization (HR 1.09; 95% CI 0.65-1.82; P=0.6260). Early and sustained reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline were observed with sacubitril/valsartan compared with enalapril (between-group difference: Week 2: 25.7%, P<0.01; Month 6: 18.9%, P=0.01, favoring sacubitril/valsartan). There was no significant difference in the changes in NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at Week 8 and Month 6. Sacubitril/valsartan was well tolerated with fewer study drug discontinuations due to adverse events, although the sacubitril/valsartan group had a higher proportion of patients with hypotension.

Conclusions: In Japanese patients with HFrEF, there was no difference in reduction in the risk of CV death or HF hospitalization between sacubitril/valsartan and enalapril, and sacubitril/valsartan was safe and well tolerated.
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http://dx.doi.org/10.1253/circj.CJ-20-0854DOI Listing
April 2021

Undiagnosed Cardiac Sarcoidosis Causing Refractory Heart Failure After Acute Myocardial Infarction due to Thromboembolism.

Int Heart J 2021 Mar 17;62(2):437-440. Epub 2021 Mar 17.

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

A 61-year-old woman suffered chest pain and was admitted to a nearby hospital emergency department. She was diagnosed with acute myocardial infarction probably due to thromboembolism in the left anterior descending coronary artery and aspiration thrombectomy was performed. Afterwards, she developed refractory heart failure with severe global left ventricular dysfunction and was transferred to our hospital. An F-FDG-PET/CT scan revealed abnormal F-FDG uptake in non-infarcted regions of the left ventricle. Non-caseating granulomas were detected by biopsy from a skin eruption. She was diagnosed with cardiac sarcoidosis. In cases of refractory heart failure which cannot be explained only by myocardial infarction, evaluation of other undiagnosed cardiomyopathies is important for optimal management.
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http://dx.doi.org/10.1536/ihj.20-586DOI Listing
March 2021

Effect of the COVID-19 Pandemic on Acute Respiratory Care of Hypoxemic Patients With Acute Heart Failure in Japan - A Cross-Sectional Study.

Circ Rep 2020 Aug 13;2(9):499-506. Epub 2020 Aug 13.

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

The effect of the COVID-19 pandemic on the respiratory management strategy with regard to the use of non-invasive positive pressure ventilation (NPPV) and high-flow nasal cannula (HFNC) in patients with acute heart failure (AHF) in Japan is unclear. This cross-sectional study used a self-reported online questionnaire, with responses from 174 institutions across Japan. More than 60% of institutions responded that the treatment of AHF patients requiring respiratory management became fairly or very difficult during the COVID-19 pandemic than earlier, with institutions in alert areas considering such treatment significantly more difficult than those in non-alert areas (P=0.004). Overall, 61.7% and 58.8% of institutions changed their indications for NPPV and HFNC, respectively. Significantly more institutions in the alert area changed their practices for the use of NPPV and HFNC during the COVID-19 pandemic (P=0.004 and P=0.002, respectively). When there was insufficient time or information to determine whether AHF patients may have concomitant COVID-19, institutions in alert areas were significantly more likely to refrain from using NPPV and HFNC than institutions in non-alert areas. The COVID-19 pandemic has compelled healthcare providers to change the respiratory management of AHF, especially in alert areas.
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http://dx.doi.org/10.1253/circrep.CR-20-0081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819655PMC
August 2020

Standard Export Data Format for Extension Storage of Standardized Structured Medical Information Exchange.

Circ Rep 2020 Sep 19;2(10):587-616. Epub 2020 Sep 19.

Jichi Medical University Tochigi Japan.

In the era of big data, the utilization and analysis of large amounts of clinical data are imperative. The standardized structured medical information exchange version 2 (SS-MIX2) is a standard data storage format used in Japan to share clinical data from various vendor-derived hospital information systems. This storage format is divided into 2 categories: standardized and extension storage. Although the standardized storage includes clinical data such as basic patient data, prescriptions, and laboratory results, all other data are stored in the extension storage, because their formats are not standardized. In 2015, the Japanese Circulation Society developed the standard export data format (SEAMAT) for electrocardiography (ECG), ultrasound cardiography (UCG), and catheterization (CATH) data for the SS-MIX2 extension storage. Using physical examination and catheter report systems in accordance with the SEAMAT, specific cardiological data such as ECG, UCG, and CATH can be transferred to the SS-MIX2 extension storage, resulting in efficient secondary use of these data for research purposes. SEAMAT can aid in the effective establishment of a nationwide clinical database, and reduce tedious manual data input by clinicians and clinical research coordinators. Moreover, a program that enables the conversion of comma-separated data from information systems into SEAMAT can provide a useful and economical tool for transferring huge clinical data to the SS-MIX2.
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http://dx.doi.org/10.1253/circrep.CR-20-0077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932821PMC
September 2020

Oral Anticoagulant Use in Elderly Japanese Patients With Non-Valvular Atrial Fibrillation - Subanalysis of the ANAFIE Registry.

Circ Rep 2020 Oct 1;2(10):552-559. Epub 2020 Oct 1.

Biostatistics & Data Management Department, Daiichi Sankyo Tokyo Japan.

Oral anticoagulants (OACs) are effective in preventing stroke in patients with atrial fibrillation (AF), but are challenging for elderly patients because of the higher risk of bleeding complications. The ANAFIE Registry is a prospective multicenter observational study of elderly (≥75 years) Japanese AF patients. This subanalysis evaluated the current use of OACs. Of 32,713 patients (mean age 81.5 years), 30,068 (91.9%) were receiving OACs, including 8,354 (25.5%) on warfarin and 21,714 (66.4%) on direct OACs (DOACs); 2,645 (8.1%) were not receiving OACs. The most common prescribed dose was a reduced dose for all DOACs. A substantial proportion of patients receiving the reduced dose did not fulfill dose reduction criteria (underdosing): apixaban, 25.1%; rivaroxaban, 26.3%; and edoxaban, 13.7%. Some patients received a lower off-label dose rather than the reduced dose: apixaban, 5.9%; rivaroxaban, 0.3%; edoxaban, 5.3%; and dabigatran, 13.6%. In multivariate analyses, advanced age, history of hemorrhage, paroxysmal AF, and antiplatelet drug use were significantly associated with no OAC. Advanced age, persistent or permanent AF, chronic kidney disease, and concomitant antiplatelet drugs were associated with warfarin rather than DOAC use. In the ANAFIE Registry, >90% of elderly Japanese AF patients received OAC therapy, mostly DOACs. Inappropriate low doses of DOACs that did not fulfill dose reduction criteria were prescribed in 20-30% of patients.
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http://dx.doi.org/10.1253/circrep.CR-20-0082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932811PMC
October 2020

Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.

J Card Fail 2021 Mar 1. Epub 2021 Mar 1.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.
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http://dx.doi.org/10.1016/j.cardfail.2021.01.022DOI Listing
March 2021

Universal Definition and Classification of Heart Failure.

J Card Fail 2021 Feb 7. Epub 2021 Feb 7.

Endorsed by Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, Chinese Heart Failure Association.

In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as: At-risk for HF (Stage A) , for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-heart failure (Stage B) for patients without current or prior symptoms or signs of HF but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C) for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D) for patients with severe symptoms and/ or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT) , refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF) . The classification includes HF with reduced EF (HFrEF) : HF with LVEF ≤ 40%; HF with mid-range EF (HFmrEF) : HF with LVEF 41-49%; HF with preserved EF (HFpEF) : HF with LVEF ≥ 50%; and HF with improved EF (HFimpEF) : HF with a baseline LVEF ≤ 40%, a ≥ 10 point increase from baseline LVEF, and a second measurement of LVEF > 40.
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http://dx.doi.org/10.1016/j.cardfail.2021.01.022DOI Listing
February 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

Comparison of Endothelial Dysfunction in Coronary Arteries with Bare Metal and 2-Generation Drug-Eluting Stents.

J Atheroscler Thromb 2021 Feb 19. Epub 2021 Feb 19.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University.

Aims: Previous studies suggested that implantation with a 1st-generation DES was associated with coronary endothelial dysfunction, which was associated with Rho-kinase activation. Second-generation drug-eluting stents (DESs) may preserve coronary endothelial function in stented coronary arteries; however, because of methodological limitations, further study is needed to clarify the association between 2-generation DESs and coronary endothelial dysfunction.

Methods: We retrospectively analysed the CuVIC trial database, where we identified 112 patients who underwent coronary stenting in the left coronary arteries with either a bare metal stent (BMS, n=53) or 2-generation DES (n=59). We compared vasomotions of target vessels with stents and non-target vessels without stents. Furthermore, we measured the Rho-kinase activation detected in mononucleocytes from aortic and coronary sinus blood.

Results: ACh-induced vasoconstrictive responses of target vessels were not enhanced with a 2-generation DES (45±21% vs. 44±20%, P=0.56, paired t-test), but significantly enhanced in the coronary arteries with a BMS (50±18% vs. 42±20%, P=0.002). Rho-kinase activation did not differ between patients with a BMS and 2-generation DES. In the target vessels with a BMS, large late lumen loss and acute coronary syndrome (ACS) at the index percutaneous coronary intervention (PCI) were associated with ACh-induced enhanced coronary vasoconstrictive responses.

Conclusions: Evaluation of ACh-induced vasomotion of target vessels comparing with non-target vessels revealed that 2-generation DESs were not associated with coronary endothelial dysfunction in target vessels, nor activation of Rho-kinase in the coronary sinus blood 6-8 months after stenting.
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http://dx.doi.org/10.5551/jat.61366DOI Listing
February 2021

Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.

Eur J Heart Fail 2021 Mar 3;23(3):352-380. Epub 2021 Mar 3.

In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.
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http://dx.doi.org/10.1002/ejhf.2115DOI Listing
March 2021