記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.4309-24

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Guideline-directed medical therapy (GDMT) is important in heart failure management; however, polypharmacy itself may impact heart failure. Although measures against polypharmacy are needed, current discussion on unilateral drug tapering (including the drugs that should be tapered) is insufficient. In this study, we investigated the relationship between the number of prescribed GDMT drugs and prognosis in patients with heart failure. METHODS: In this single-centre retrospective study, 3,146 eligible patients with heart failure were included and divided into four groups based on the median number of prescribed GDMT drugs and the median number of drugs not included in the GDMT (ni-GDMT) at the time of hospital discharge. The definition of GDMT was based on various Japanese guidelines. The primary outcome was all-cause mortality within 3 years of hospital discharge. RESULTS: A total of 252 deaths were observed during the 3-year follow-up period. Kaplan-Meier analysis revealed that groups with GDMT drug count ≥ 5 and ni-GDMT drug count < 4 had the lowest mortality, and those with GDMT drug count < 5 and ni-GDMT drug count ≥ 4 had the highest mortality (log-rank, P < 0.001). Cox regression analysis revealed a significant association between ni-GDMT drug count and all-cause mortality, even after adjustment for number of GDMT medications, age, male, left ventricular ejection function < 40%, hemoglobin, albumin levels, and estimated glomerular filtration rate [HR = 1.06 (95% CI: 1.01-1.11), P = 0.020]. Conversely, the GDMT drug count was not associated with increased mortality rates. CONCLUSIONS: The ni-GDMT drug count was significantly associated with 3-year mortality in patients with heart failure. Conversely, the GDMT drug count did not worsen the prognosis. Polypharmacy measures should consider ni-GDMT drug quantity to improve the prognosis and outcomes in patients with heart failure.

DOI： 10.1186/s40780-024-00357-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of the present study is to elucidate prognostic impact of temporal trends of non-surgical patients requiring intensive care over a 10-year period. METHODS AND RESULTS: A total of 4276 non-surgical patients requiring intensive care from 2012 to 2021 were enrolled. Patients' backgrounds, in-hospital management, and prognoses were compared between five groups [2012-2013 (n = 825), 2014-2015 (n = 784), 2016-2017 (n = 864), 2018-2019 (n = 939), and 2020-2021 (n = 867)]. During the study period, mean age significantly increased from 69 years in 2012-2013 to 72 years in 2020-2021. Mean Acute Physiology and Chronic Health Evaluation scores significantly increased from 10 points in 2012-2013 to 12 points in 2020-2021. The median duration of intensive care unit stays increased from 3 to 4 days. Kaplan-Meier survival curve analysis showed that survival rates during 30- and 365-days were significantly lower in 2020-2021 than in 2012-2013, but it was not significantly different by a Cox proportional hazards regression model in 30 days. A Cox proportional hazards regression model revealed that the risks of 365-day all-cause death were significantly higher in patients enrolled in 2016-2017 (HR: 1.324, 95 % CI: 1.042-1.680, p = 0.021), in 2018-2019 (HR: 1.329, 95 % CI: 1.044-1.691, p = 0.021), and in 2020-2021 (HR: 1.409, 95 % CI: 1.115-1.779, p = 0.004). CONCLUSION: The condition of patients requiring intensive care is becoming more critical year by year, leading to poorer long-term prognoses despite improvements in treatment strategies. These findings emphasize the importance of additional care management after admission into non-surgical intensive care units, particularly for the aging society of Japan.

DOI： 10.1016/j.jjcc.2024.06.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Although takotsubo syndrome (TTS) is characterized by transient systolic dysfunction of the left ventricle (LV), the time course and mechanism of LV function recovery remain elusive. The aim of this study is to evaluate cardiac functional recovery in TTS via serial cardiac magnetic resonance feature tracking (CMR-FT). Methods: In this Japanese multicenter registry, patients with newly diagnosed TTS were prospectively enrolled. In patients who underwent serial cardiovascular magnetic resonance (CMR) imaging at 1 month and 1 year after the onset, CMR-FT was performed to determine the global circumferential strain (GCS), global radial strain (GRS) and global longitudinal strain (GLS). We compared LV ejection fraction, GCS, GRS and GLS at 1 month and 1 year after the onset of TTS. Results: Eighteen patients underwent CMR imaging in one month and one year after the onset in the present study. LV ejection fraction had already normalized at 1 month after the onset, with no significant difference between 1 month and 1 year (55.8 ± 9.2% vs. 58.9 ± 7.3%, p = 0.09). CMR-FT demonstrated significant improvement in GCS from 1 month to 1 year (-16.7 ± 3.4% vs. -18.5 ± 3.2%, p < 0.01), while there was no significant difference in GRS and GLS between 1 month and year (GRS: 59.6 ± 24.2% vs. 59.4 ± 17.3%, p = 0.95, GLS: -12.8 ± 5.9% vs. -13.8 ± 4.9%, p = 0.42). Conclusions: Serial CMR-FT analysis revealed delayed improvement of GCS compared to GRS and GLS despite of rapid recovery of LV ejection fraction. CMR-FT can detect subtle impairment of LV systolic function during the recovery process in patients with TTS.

DOI： 10.3390/jcm13113238

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Plasma volume status (PVS), a measure of plasma volume, has been evaluated as a prognostic marker for chronic heart failure. Although the prognostic value of PVS has been reported, its significance in patients with acute decompensated heart failure (ADHF) admitted to the cardiovascular intensive care unit (CICU) remains unclear. In this study, we examined the relationship between PVS and long-term mortality in patients with ADHF admitted to the CICU. METHODS: Between January 2018 and December 2020, 363 consecutive patients with ADHF were admitted to the Nippon Medical School Hospital CICU. Of the 363 patients, 206 (mean age, 74.9 ± 12.9 years; men, 64.6%) were enrolled in this study. Patients who received red blood cell transfusions, underwent dialysis, were discharged from the CICU or died in the hospital were excluded from the study. We measured the PVS of the patients at admission, transfer to the general ward (GW) and discharge using the Kaplan-Hakim formula. The patients were assigned to four groups according to the quartiles of their PVS measured at each of the three abovementioned timepoints. We examined the association between PVS and all-cause mortality during the observation period (1134 days). The primary endpoint of this study was all-cause mortality. RESULTS: The Kaplan-Meier analysis showed that the high PVS group had a significantly higher mortality rate at admission, transfer to the GW and discharge than the other groups (log-rank test: P = 0.016, P = 0.005 and P < 0.001, respectively). Univariate Cox regression analysis showed that age, body mass index, history of heart failure, use of beta-blockers, albumin level, blood urea nitrogen level, N-terminal pro-brain natriuretic peptide level and left ventricular ejection fraction were significantly different among the PVS groups and thus were not significant prognostic factors for ADHF. Furthermore, the multivariate analysis revealed that PVS at discharge [hazard ratio (HR) = 1.06 (1.00-1.12), P = 0.048] was an independent poor prognostic factor for ADHF. CONCLUSIONS: This study highlights the effect of PVS measured at different timepoints on the prognoses of ADHF patients. Regular assessment of PVS, particularly at discharge, is crucial for optimising patient management and achieving favourable outcomes in cases of ADHF.

DOI： 10.1002/ehf2.14874

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pimobendan reportedly improves the subjective symptoms of heart failure. However, evidence of improved prognosis is lacking. This study aimed to determine whether reinforcing guideline-directed medical therapy (GDMT) improved rehospitalization rates for worsening heart failure in patients administered pimobendan. METHODS: A total of 175 patients with heart failure who were urgently admitted to our hospital for worsening heart failure and who received pimobendan between January 2015 and February 2022 were included. Of the 175 patients, 44 were excluded because of in-hospital death at the time of pimobendan induction. The remaining 131 patients were divided into two groups, the reduced ejection fraction (rEF) (n = 93) and non-rEF (n = 38) groups, and further divided into the GDMT-reinforced and non-reinforced groups. RESULTS: In patients with rEF, the rate of rehospitalization for heart failure was significantly lower in the GDMT-reinforced group than in the non-reinforced group (log-rank test, P = .04). However, the same trend was not observed in the non-rEF group. CONCLUSIONS: Reinforcing GDMT may reduce the heart failure rehospitalization rate in patients with pimobendan administration and rEF. However, multicenter collaborative research is needed. TRIAL REGISTRATION: IRB Approval by the Nippon Medical School Hospital Ethics Committee B-2021-433 (April 10, 2023).

DOI： 10.1186/s40780-024-00346-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Sleep-disordered breathing (SDB) is closely related to cardiovascular diseases. The higher the apnoea-hypopnoea index (AHI), the higher the prevalence of cardiovascular diseases. Despite these findings suggesting a close link between SDB and heart failure, the relationship between the severity of SDB and the onset of heart failure symptoms in individuals without apparent heart failure symptoms (Heart Failure Stage A + B) remains poorly understood. METHODS AND RESULTS: Between December 2010 and June 2017, we conducted full-night polysomnography (PSG) at the Nippon Medical School Chiba Hokusoh Hospital, extracting patients who were at risk of heart failure (Stage A or B in the Heart Failure Guidelines). Using a median cut-off of AHI ≥ 41.6 events/hour, we divided the patients into two groups and examined the composite endpoint of all-cause mortality plus hospitalization due to heart failure as the primary endpoint. We included 230 patients (mean age 63.0 ± 12.5 years, 78.3% males) meeting the selection criteria. When comparing the two groups, those with AHI < 41.6 events/hour (L group, n = 115) and those with AHI ≥ 41.6 events/hour (H group, n = 115), the H group had higher body mass index and higher serum triglyceride, and lower the frequency of acute coronary syndrome and lower estimated glomerular filtration rate than did the L group, but no other patient characteristics differed significantly. The H group had a significantly higher incidence of the composite endpoint than did the L group (10.6% vs. 2.6%, P = 0.027). Factors associated with the composite endpoint were identified through multivariate analyses, with AHI, haemoglobin, and left atrial dimension emerging as significant factors (hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 1.00-1.04, P = 0.024; HR = 0.71, 95% CI = 0.54-0.94, P = 0.017; and HR = 1.10, 95% CI = 1.03-1.18, P = 0.006, respectively). Conversely, the minimum SpO2 during PSG (<80%) was not associated with the composite endpoint. CONCLUSIONS: In patients with SDB who are at risk of heart failure, severe SDB is associated with a high risk of all-cause mortality and the development of heart failure. Additionally, combining cardiac echocardiography and PSG data may improve risk stratification, offering potential assistance for early intervention. Further examination with a validation cohort is necessary.

DOI： 10.1002/ehf2.14824

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ehjci/jead341

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Heart Journal (Japanese Heart Journal)  

Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.

DOI： 10.1536/ihj.23-596

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Peripheral artery disease (PAD) compromises walking and physical activity, which results in further loss of skeletal muscle. The cross-sectional area of the thigh muscle has been shown to be correlated with systemic skeletal muscle volume. In our previous pilot study, we observed an increase in thigh muscle mass following endovascular treatment (EVT) in patients with proximal vascular lesions affecting the aortoiliac and femoropopliteal arteries. Considering the potential interactions between skeletal muscle, lipid profile, and glucose metabolism, we aimed to investigate the relationship between thigh muscle mass and apolipoproteins as well as glucose metabolism in PAD patients undergoing EVT. This study is a prespecified sub-study conducted as part of a pilot study. We prospectively enrolled 22 symptomatic patients with peripheral artery disease (PAD) and above-the-knee lesions, specifically involving the blood vessels supplying the thigh muscle. The mid-thigh muscle area was measured with computed tomography before and 6 months after undergoing EVT. Concurrently, we measured levels of apolipoproteins A1 (Apo A1) and B (Apo B), fasting blood glucose, 2 h post-load blood glucose (using a 75 g oral glucose tolerance test), and glycated hemoglobin A1c (HbA1c). Changes in thigh muscle area (delta muscle area: 2.5 ± 8.1 cm2) did not show significant correlations with changes in Apo A1, Apo B, fasting glucose, 2 h post-oral glucose tolerance test blood glucose, HbA1c, or Rutherford classification. However, among patients who experienced an increase in thigh muscle area following EVT (delta muscle area: 8.41 ± 5.93 cm2), there was a significant increase in Apo A1 (pre: 121.8 ± 15.1 mg/dL, 6 months: 136.5 ± 19.5 mg/dL, p &lt; 0.001), while Apo B remained unchanged (pre: 76.4 ± 19.2 mg/dL, 6 months: 80.5 ± 4.9 mg/dL). Additionally, post-oral glucose tolerance test 2 h blood glucose levels showed a decrease (pre: 189.7 ± 67.5 mg/dL, 6 months: 170.6 ± 69.7 mg/dL, p = 0.075). Patients who exhibited an increase in thigh muscle area demonstrated more favorable metabolic changes compared to those with a decrease in thigh muscle area (delta muscle area: −4.67 ± 2.41 cm2). This pilot sub-study provides insights into the effects of EVT on thigh muscle, apolipoproteins, and glucose metabolism in patients with PAD and above-the-knee lesions. Further studies are warranted to validate these findings and establish their clinical significance. The trial was registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN000047534).

DOI： 10.3390/metabo14040192

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aims

Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF).

Methods and results

Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, &gt;32.1% and ≤38.0%; and high, &gt;38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut‐off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow‐up, 170 HF readmissions occurred. Kaplan–Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log‐rank test, P &lt; 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission.

Conclusions

The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF.

DOI： 10.1002/ehf2.14755

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

Background: Although the clinical factors that predict major bleeding in Western patients with acute coronary syndrome (ACS) are becoming elucidated, they have not been fully investigated, especially coronary lesion characteristics, in a Japanese population. Methods and Results: ACS patients (n=1,840) were divided into a "bleeding group" and a "no-bleeding group," according to whether they had major bleeding during the 2-year follow-up period, to investigate the prognostic effect of bleeding and the predictive factors of bleeding. Among them, patients who underwent primary percutaneous coronary intervention with optical coherence tomography (OCT) guidance (n=958) were examined to identify the effect of coronary lesion characteristics on bleeding. Of the 1,840 enrolled patients, 124 (6.7%) experienced major bleeding during the 2-year follow-up period. Incidence of cardiovascular death during the 2-year follow-up period was significantly higher among patients with major bleeding (26.4% vs. 8.5%, P=0.001). OCT examination showed that disrupted fibrous cap (DFC: 68% vs. 48%, P=0.014) and calcified plaque (63% vs. 42%, P=0.011) were more prevalent in the bleeding group. DFC was a predictor of major bleeding in the multivariate Cox proportional hazards analyses (hazard ratio 2.135 [95% confidence interval 1.070-4.263], P<0.001). Conclusions: ACS patients with major bleeding had poorer cardiac outcomes. Advanced atherosclerosis at the culprit lesion influences the higher incidence of major bleeding in ACS patients.

DOI： 10.1253/circrep.CR-24-0003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.3487-24

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ehjci/jeae004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Ventricular tachycardia (VT) associated with primary cardiac tumors (PCTs) originating from the ventricles is rare, but lethal, in young patients. OBJECTIVES: This study aimed to clarify the mechanisms underlying primary cardiac tumor-related ventricular tachycardia (PCT-VT) and establish a therapeutic strategy for this form of VT. METHODS: Among 67 patients who underwent surgery for VT at our institute between 1981 and 2020, 4 patients aged 1 to 34 years, including 3 males, showed PCT-VT (fibroma, 2; lipoma, 1; and hamartoma, 1), which was investigated using a combination of intraoperative electroanatomical mapping and histopathological studies. RESULTS: All 4 patients developed electrical storms of sustained VTs refractory to multiple drugs and repetitive endocardial ablations. The VT mechanism was re-entry, and intraoperative electroanatomical mapping showed a centrifugal activation pattern originating from the border between the tumor and healthy myocardium, where fractionated potentials were detected during sinus rhythm. Histopathological studies of serial sections of specimens acquired from these areas revealed tumor infiltration into the surrounding myocardium with cell disorganization, exhibiting myocardial disarray. Several myocardia entrapped in the tumor edges contributed to the development and sustainment of re-entrant VT activation. In the 2 patients in whom complete resection was unfeasible, encircling cryoablation to entirely isolate the unresectable tumor was effective in suppressing VT occurrence. CONCLUSIONS: The mechanism underlying PCT-VT involves re-entry localized at the tumor edges. Myocardial disarray associated with tumor infiltration is a substrate for this form of VT. Cryoablation along the border between the tumor and myocardium is a promising therapeutic option for unresectable PCT-VT.

DOI： 10.1016/j.jacep.2023.08.033

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

DOI： 10.1093/ehjcr/ytae025

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その他リンク： https://academic.oup.com/ehjcr/article-pdf/8/1/ytae025/56397918/ytae025.pdf

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.23-564

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The evaluation of triglyceride-glucose (TyG) index has not been sufficient in patients requiring nonsurgical intensive care.A total of 3,906 patients who required intensive care were enrolled. We computed the TyG index using the value on admission by the following formula: ln [triglyceride (mg/dL) × glucose (mg/dL) /2]. Patients were divided into three groups according to the TyG index quartiles: low (quartile 1 [Q1]; TyG index ≤ 8.493, n = 977), middle (Q2/Q3; 8.494 ≤ TyG index ≤ 9.536, n = 1,953), and high (Q4; TyG index > 9.537, n = 976). The median (interquartile range) TyG index was 9.00 (8.50-9.54); acute coronary syndrome (ACS) had the highest TyG index among all etiologies at 9.12 (8.60-9.68). A multivariate logistic regression model showed that ACS (odds ratio [OR], 2.133; 95% confidence interval [CI], 1.783-2.552) were independently correlated with high TyG index. A Cox proportional hazards regression model revealed that, in ACS, the Q2/Q3 and Q4 groups were independent predictors of 30-day all-cause mortality (hazard ratio [HR], 1.778; 95% CI, 1.014-3.118; HR, 2.986; 95% CI, 1.680-5.308; respectively) and that in acute heart failure [AHF], the Q4 group was a converse independent predictor of 30-day all-cause mortality (HR, 0.488; 95% CI, 0.241-0.988).High TyG index was linked to ACS and negative outcomes in the ACS group; in contrast, low TyG index was associated with adverse outcomes in the AHF group.

DOI： 10.1536/ihj.23-409

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

DOI： 10.1536/ihj.23-603

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cardiogenic shock is a complex and diverse pathological condition characterized by reduced myocardial contractility. The goal of treatment of cardiogenic shock is to improve abnormal hemodynamics and maintain adequate tissue perfusion in organs. If hypotension and insufficient tissue perfusion persist despite initial therapy, temporary mechanical circulatory support (t-MCS) should be initiated. This decade sees the beginning of a new era of cardiogenic shock management using t-MCS through the accumulated experience with use of intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO), as well as new revolutionary devices or systems such as transvalvular axial flow pump (Impella) and a combination of VA-ECMO and Impella (ECPELLA) based on the knowledge of circulatory physiology. In this transitional period, we outline the approach to the management of cardiogenic shock by t-MCS. The management strategy involves carefully selecting one or a combination of the t-MCS devices, taking into account the characteristics of each device and the specific pathological condition. This selection is guided by monitoring of hemodynamics, classification of shock stage, risk stratification, and coordinated management by the multidisciplinary shock team.

DOI： 10.1186/s40560-023-00710-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Although catheter ablation (CA) of tachycardia-bradycardia syndrome (TBS) in patients with atrial fibrillation (AF) is considered to be an effective treatment strategy, pacemaker implantations (PMIs) are often required even after a successful CA. This study aimed to elucidate the clinical predictors of a PMI after CA. METHODS: From 2011 to 2020, 103 consecutive patients diagnosed with TBS were retrospectively enrolled in the study. Among the 103 patients, 54 underwent a PMI and 49 CA of AF. During 47.4 ± 35.4 months after 1.4 ± 0.6 CA sessions, 37 (75.5%) of 49 patients were free from atrial arrhythmia recurrences. PMIs were performed in 11 patients (PMI group) and the remaining 38 did not receive a PMI (non-PMI group). RESULTS: When comparing the PMI and non-PMI groups, there were no differences in the basic mean heart rate (P = 0.36), maximum pauses detected by 24-hour Holter-monitoring (P = 0.61), and other clinical parameters between the two groups while the right atrial area index was larger (42.1 ± 24.0 vs. 21.8 ± 8.4 cm2/m2 P = 0.002) in the PMI group than non-PMI group. The ROC curve analysis showed that the optimal cutoff point of the ratio of the right atrial area index to the left atrial area index for predicting a PMI following CA was 0.812 (Sensitivity 72.7%, specificity 71.1%, positive predictive value 42.1%, negative predictive value 90.0%, diagnostic accuracy 71.4%, AUC = 0.81). CONCLUSION: Right atrial enlargement prior to CA was considered to be one of the risk factors for a PMI after CA of AF.

DOI： 10.1016/j.ijcha.2023.101297

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ehjci/jead167

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The degree and timing of acute kidney injury (AKI) on admission and during hospitalization in patients requiring non-surgical intensive care remain unclear.Methods and Results: In this study, 3,758 patients requiring intensive care were analyzed retrospectively. AKI was defined based on the ratio of serum creatinine concentrations recorded at each time point (i.e., on admission and during the first 5 days in the intensive care unit and during hospitalization) to those measured at baseline. Patients were grouped by combining AKI severity (RIFLE class) and timing (i.e., from admission to 5 days [A-5D]; from 5 days to hospital discharge [5D-HD]) as follows: No-AKI; New-AKI (no AKI to Class R [risk; ≥1.5-fold increase in serum creatinine], I [injury; ≥2.0-fold increase in serum creatinine], and F [failure; ≥3.0-fold increase in serum creatinine or receiving dialysis during hospitalization]); Stable-AKI (Class R to R; Class I to I); and Worsening-AKI (Class R to I or F; Class I to F). Multivariate logistic regression analysis indicated that 730-day mortality was independently associated with Class R, I, and F on admission; Class I and F during the 5D-H period; and New-AKI and Worsening-AKI during A-5D and 5D-HD. CONCLUSIONS: AKI on admission, even Class R, was associated with a poor prognosis. An increase in RIFLE class during hospitalization was identified as an important factor for poor prognosis in patients requiring intensive care.

DOI： 10.1253/circj.CJ-23-0320

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0140-6736(23)01675-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We aimed to examine the relationship of living arrangements (i.e., living alone or living with others) with background, clinical severity, preintervention culprit lesion plaque morphology, and clinical outcomes in patients with acute coronary syndrome (ACS). Among 1,683 consecutive patients with ACS, we retrospectively compared patients living alone ( n  = 318) versus living with others ( n  = 1,362). Optical coherence tomography (OCT) findings, which are high-resolution intracoronary imaging devices, were analyzed in patients with preintervention OCT and compared between patients living alone ( n  = 174) versus those living with others ( n  = 665). Older (median; 69 vs. 67 y, p  = 0.046) and female (31 vs. 17%, p  < 0.001) patients more frequently lived alone. Frequency of achieving a time interval of 6 hours or less from ACS onset to admission was lower in patients living alone (56 vs. 63%, p  = 0.022). Clinical presentation was more severe in patients living alone (Killip II/III/IV; 27 vs. 22%, p  = 0.029). Plaque morphology evaluated by OCT was similar between groups (plaque rapture; 48 vs. 48%, p  = 0.171). Kaplan-Meier analyses revealed higher rates of cardiac mortality during 2-year follow-up period in patients living alone [13.9 vs. 8.5%, hazard ratio (HR) 1.604, 95% confidence interval (CI) 1.112-2.313, p  = 0.010]. After traditional cardiovascular risk factors and clinical severity upon admission had been adjusted, living alone was an independent predictor of cardiac mortality in ACS patients (HR 1.582, 95% CI 1.056-2.371, p  = 0.026). Living alone was independently associated with 2-year cardiacmortality in ACS patients after adjusting for background and presentation and might be unrelated to the development of atherosclerosis.

DOI： 10.1055/s-0043-1767697

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Cardiac resynchronization therapy (CRT) is well-established for treating symptomatic heart failure with electrical dyssynchrony. The left ventricular (LV) lead position is recommended at LV posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients being upgraded from right ventricular (RV) apical pacing to CRT. This study aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT. METHODS: We used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and posterolateral sites during RV apical pacing. Simultaneous biventricular pacing was performed at the RV apex and each LV site, and the differences in QRS duration and LV dP/dtmax from those of RV apical pacing were measured. RESULTS: Thirty-seven patients with anterolateral and posterolateral LV CS branches were included. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90 ± 0.06 vs. 0.71 ± 0.11, p < .001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dtmax were higher at the LV anterolateral site than at the posterolateral site (45.7 ± 18.0% vs. 32.0 ± 17.6%, p < .001; 12.7 ± 2.9% vs. 3.7 ± 8.2%, p < .001, respectively) during biventricular pacing compared with RV apical pacing. CONCLUSION: The LV anterolateral site is the preferred LV lead position in patients being upgraded from conventional RV apical pacing to CRT.

DOI： 10.1111/jce.16005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with hypertrophic cardiomyopathy (HCM) may progress to the dilated phase (DHCM). This study aimed to identify the predictive factors for DHCM progression, including left ventricular (LV) ejection fraction (LVEF < 50%) or decreased LV contraction (LVEF < 60%). The study included 291 patients enrolled in our hospital's HCM registry who were grouped based on their poststudy LVEF (LVEF of ≥60%, 50-59%, and <50%). Predictive factors of an LVEF of <50% or <60% were determined. Further, the effects of percutaneous transluminal septal myocardial ablation (PTSMA) on long-term systolic LV function and DHCM development were investigated. LVEF was ≥60%, 50-59%, and <50% in 239, 33, and 19 patients, respectively, during the follow-up period (mean: 64.9 months). Multivariate analyses indicated baseline atrial fibrillation (AF), nonsustained ventricular tachycardia (NSVT), and left ventricular diameter at end-systole (LVDs) as significant predictors of DHCM. Using a scoring method based on AF, NSVT, and LVDs, patients with 2 and 3 points had a significantly higher risk of developing DHCM. PTSMA in 78 HCM patients demonstrated no significant effect on long-term LVEF changes or DHCM development. We concluded that AF, NSVT, and LVDs are significant predictors of DHCM development. However, a validation study with a larger population is required.

DOI： 10.3390/jcm12155137

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This retrospective observational study aimed to examine the relationships of maximum walking speed (MWS) with peak oxygen uptake (peak VO2) and anaerobic threshold (AT) obtained by cardiopulmonary exercise testing (CPX) in patients with heart failure. The study participants were 104 consecutive men aged ≥ 20 years who had been hospitalized or had undergone outpatient care at our hospital for heart failure between February 2019 and January 2023. MWS was measured in a 5-m section with a 1-m run-up before and after the course. Multivariable analysis was used to examine the association between MWS and peak VO2 and AT by CPX. The Pearson correlation coefficient showed that MWS was positively correlated with percent-predicted peak VO2 and percent-predicted AT (r = 0.463, p < 0.001; and r = 0.485, p < 0.001, respectively). In the multiple linear regression analysis employing percent-predicted peak VO2 and percent-predicted AT as the objective variables, only MWS demonstrated a significant positive correlation (standardized β: 0.471, p < 0.001 and 0.362, p < 0.001, respectively). Multiple logistic regression analyses, using an 80% cutoff in percent-predicted peak VO2 and AT, revealed that only MWS was identified as a significant factor in both cases (odds ratio [OR]: 1.239, 95% confidence interval [CI]: 1.071-1.432, p = 0.004 and OR: 1.469, 95% CI: 1.194-1.807, p < 0.001, respectively). MWS was correlated with peak VO2 and AT in male patients with heart failure. The MWS measurement as a screening test for exercise tolerance may provide a simple means of estimating peak VO2 and AT in heart failure patients.

DOI： 10.1007/s00380-023-02289-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cardiogenic shock (CS) is caused by primary cardiac dysfunction and induced by various and heterogeneous diseases (e.g., acute impairment of cardiac performance, or acute or chronic impairment of cardiac performance). MAIN BODY: Although a low cardiac index is a common finding in patients with CS, the ventricular preload, pulmonary capillary wedge pressure, central venous pressure, and systemic vascular resistance might vary between patients. Organ dysfunction has traditionally been attributed to the hypoperfusion of the organ due to either progressive impairment of the cardiac output or intravascular volume depletion secondary to CS. However, research attention has recently shifted from this cardiac output ("forward failure") to venous congestion ("backward failure") as the most important hemodynamic determinant. Both hypoperfusion and/or venous congestion by CS could lead to injury, impairment, and failure of target organs (i.e., heart, lungs, kidney, liver, intestines, brain); these effects are associated with an increased mortality rate. Treatment strategies for the prevention, reduction, and reversal of organ injury are warranted to improve morbidity in these patients. The present review summarizes recent data regarding organ dysfunction, injury, and failure. CONCLUSIONS: Early identification and treatment of organ dysfunction, along with hemodynamic stabilization, are key components of the management of patients with CS.

DOI： 10.1186/s40560-023-00676-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND: Hypoalbuminemia is common in critically ill patients and is associated with poor outcomes. However, the relationship between serum albumin levels and clinical outcomes in patients with takotsubo syndrome remains unclear. We examined the impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome. METHODS: Using the multicenter registry of the Tokyo Cardiovascular Care Unit Network between January 2017 and December 2020, we identified 631 eligible patients with takotsubo syndrome (median age, 78 years; male proportion, 22 %) and documented serum albumin levels at admission, which were used to allocate patients to hypoalbuminemia (serum albumin <3.5 g/dL) or normal albumin (serum albumin ≥3.5 g/dL) groups. Patient characteristics and in-hospital mortality were compared between the groups. RESULTS: Hypoalbuminemia was detected in 200 (32 %) patients at admission. The hypoalbuminemia group was older and had a higher proportion of men and preceding physical triggers than the normal albumin group. In-hospital all-cause mortality was greater in the hypoalbuminemia group than in the normal albumin group (9.5 % vs. 1.9 %, p < 0.001). Both cardiac (3.0 % vs. 0.5 %, p = 0.015) and non-cardiac (6.5 % vs. 1.4 %, p = 0.002) mortality was greater in the hypoalbuminemia group. In multivariable logistic regression analysis, hypoalbuminemia was independently associated with increased in-hospital mortality, even after adjusting for confounders, including age, sex, and triggering events (odds ratio, 3.23; 95 % confidence interval, 1.31-7.95; p = 0.011). CONCLUSIONS: In patients with takotsubo syndrome, hypoalbuminemia is a common comorbidity and is associated with a substantial risk of in-hospital death. Close monitoring and comprehensive critical care are required in these patients.

DOI： 10.1016/j.jjcc.2023.06.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The time-dependent changes in the natriuretic peptide families during sacubitril/valsartan (S/V) treatment remain obscure in the Asian heart failure (HF) cohort. Eighty-one outpatients with compensated HF were analyzed. The patients were divided into two groups based on the administration of S/V (n = 42) or angiotensin converting enzyme inhibitor (ACE-I; n = 39). Changes to the natriuretic peptide families and the daily dose of loop diuretics were evaluated 3 and 6 months after the intervention. The atrial natriuretic peptide (ANP) level was significantly increased (102 [63-160] pg/mL to 283 [171-614] pg/mL [3 months]; 409 [210-726] pg/mL [6 months]) in the S/V group but not in the ACE-I group. The dose of furosemide was significantly decreased during the six-month follow-up period in the S/V group (40 [20-40] mg to 20 [10-20] mg) but not in the ACE-I group. A multivariate logistic regression model showed that the presence of persistent atrial fibrillation (AF) and HF with a preserved left ventricular ejection fraction (HFpEF) was independently associated with a high delta-ANP ratio (≥ 4.5 ANP value on the start date/ANP value at 6 months; the mean value was used as the cutoff value) (odds ratio [OR]: 4.649, 95% CI 1.032-20.952 and OR: 7.558, 95% CI 1.427-40.042). The plasma level of ANP was increased, and the loop diuretic dose was decreased by the addition of neprilysin inhibitor therapy in patients with compensated HF. In patients with HFpEF and complicated persistent AF, neprilysin inhibitor therapy was associated with an increase in ANP.

DOI： 10.1007/s00380-022-02230-9

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記述言語：英語  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Maintenance of euvolaemia with diuretics is critical in heart failure (HF) patients with chronic kidney disease (CKD); however, it is challenging because no reliable marker of volume status exists. Fractional excretion of urea nitrogen (FEUN) is a useful index of volume status in patients with renal failure. We aimed to examine whether FEUN is a surrogate marker of volume status for risk stratification in HF patients with CKD. METHODS AND RESULTS: We examined 516 HF patients with CKD (defined as discharge estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) whose FEUN was measured at discharge (median age, 80 years; 58% male). The patients were divided into four groups according to quartile FEUN value at discharge: low-FEUN, FEUN ≤ 32.1; medium-FEUN, 32.1 < FEUN ≤ 38.0; high-FEUN, 38.0 < FEUN ≤ 43.7; and extremely-high-FEUN, FEUN > 43.7. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). During the 3 year follow-up, 131 HF readmissions occurred. Kaplan-Meier analysis showed that the HF readmission rate was significantly lower in the medium-FEUN group than in the other three groups (log-rank test, P = 0.029). Multivariate Cox regression analysis identified the low-FEUN, high-FEUN, and extremely-high-FEUN values as independent factors associated with post-discharge HF readmission. In the analysis of 130 patients who underwent right heart catheterization during hospitalization, a significant correlation between FEUN value and right atrial pressure was observed (R = 0.243, P = 0.005). Multivariate linear regression analysis revealed that FEUN value at discharge decreased in a dose-dependent manner with loop diuretics. CONCLUSIONS: In HF patients with CKD, FEUN is a potential marker of volume status for risk stratification of post-discharge HF readmission. Low FEUN value (FEUN ≤ 32.1) may represent intravascular dehydration, whereas high FEUN value (FEUN > 38.0) may represent residual congestion; both of them were independent risk factors for HF readmission. FEUN may be useful to determine euvolaemia and guide fluid management in HF patients with CKD.

DOI： 10.1002/ehf2.14327

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Patients with acute myocardial infarction (AMI) triaged as life-threatening are transferred to our emergency medical care center (EMCC). However, data on these patients remain limited. We aimed to compare the characteristics and AMI prognosis of patients transferred to our EMCC with those transferred to our cardiovascular intensive care unit (CICU) using whole and propensity-matched cohorts.We analyzed the data of 256 consecutive AMI patients transferred from the scene to our hospital by ambulance between 2014 and 2017. The EMCC and CICU groups comprised 77 and 179 patients, respectively. There were no significant between-group age or sex differences. Patients in the EMCC group had more disease severity score and had the left main trunk identified as the culprit more frequently (12% versus 0.6%, P < 0.001) than those in the CICU group; however, the number of patients with multiple culprit vessels did not differ. The EMCC group had a longer door-to-reperfusion time (75 [60, 109] minutes versus 60 [40, 86] minutes, P< 0.001) and a higher in-hospital mortality (19% versus 4.5%, P < 0.001), especially from non-cardiac causes (10% versus 0.6%, P < 0.001), than the CICU group. However, peak myocardial creatine phosphokinase did not significantly differ between the groups. The EMCC group had a significantly higher 1-year post-discharge mortality than the CICU group (log-rank, P = 0.032); this trend was maintained after propensity score matching, although the difference was not statistically significant (log-rank, P = 0.094).AMI patients transferred to the EMCC exhibited more severe disease and worse overall in-hospital and non-cardiac mortality than those transferred to the CICU.

DOI： 10.1536/ihj.22-654

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although the primary percutaneous coronary intervention (PCI) is an established treatment for acute ST-elevation myocardial infarction (STEMI), relevant guidelines do not recommend it for recent-STEMI cases with a totally occluded infarcted related artery (IRA). However, PCI is allowed in Japan for recent-STEMI cases, but little is known regarding its outcomes. We aimed to examine the details and outcomes of PCI procedures in recent-STEMI cases with a totally occluded IRA and compared the findings with those in acute-STEMI cases.Among the 903 consecutive patients admitted with acute coronary syndrome, 250 were treated with PCI for type I STEMI with a totally occluded IRA. According to the time between symptom onset and diagnosis, patients were divided into the recent-STEMI (n = 32) and acute-STEMI (n = 218) groups. The background, procedure details, and short-term outcomes were analyzed. No significant differences between the groups were noted regarding patient demographics, acute myocardial infarction severity, or IRA distribution. Although the stent number and type were similar, significant differences were observed among PCI procedures, including the number of guidewires used, rate of microcatheter or double-lumen catheter use, and application rate of thrombus aspiration. The thrombolysis rate in the myocardial infarction flow 3-grade post-PCI did not differ significantly between the groups. Both groups had a low frequency of procedure-related complications. The in-hospital mortality rates were 0% and 4.6% in the recent-STEMI and acute-STEMI groups, respectively (P > 0.05).Although recent-STEMI cases required complicated PCI techniques, their safety, success rate, and in-hospital mortality were comparable to those of acute-STEMI cases.

DOI： 10.1536/ihj.22-656

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 77-year-old female presented with loss of consciousness, blood pressure of 90/60 mmHg, and heart rate of 47 bpm. At admission, highly sensitive Trop-T and lactate were elevated, and an electrocardiogram revealed an infero-posterior ST elevation myocardial infarction. Echocardiography revealed a depressed left ventricular ejection fraction with abnormal wall motion in the infero-posterior region and hyperkinetic apical movement along with severe mitral regurgitation (MR). Coronary angiography showed a hypoplastic right coronary artery, 100% thrombotic occlusion of the dominant left circumflex (LCx) artery, and 75% stenosis in the left anterior descending (LAD) artery. Substantial hemodynamic improvement with the reduction of acute ischemic MR was achieved by the initiation of an Impella 2.5, which is a transvalvular axial flow pump, and successful percutaneous coronary intervention (PCI) was conducted with stents to the LCx. The patient was weaned off the Impella 2.5 in 5 days, received staged PCI to LAD, and was later discharged after completion of the staged PCI to LAD.

DOI： 10.1536/ihj.22-572

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Plasma xanthine oxidoreductase (XOR) activity in patients with cardiopulmonary arrest (CPA) has not yet been studied.A total of 1,158 patients who required intensive care and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analyzed. Blood samples were collected within 15 minutes of admission from patients in intensive care patients, which were divided into a CPA group (n = 1,053) and a no-CPA group (n = 105). Plasma XOR activity was compared between the 3 groups and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the CPA group (median, 1,030.0 pmol/hour/mL; range, 233.0-4,240.0 pmol/hour/mL) was significantly higher than in the no-CPA group (median, 60.2 pmol/hour/mL; range, 22.5-205.0 pmol/hour/mL) and control group (median, 45.2 pmol/hour/mL; range, 19.3-98.8 pmol/hour/mL). The regression model showed that out-of-hospital cardiac arrest (OHCA) (yes, odds ratio [OR]: 2.548; 95% confidence interval [CI]: 1.098-5.914; P = 0.029) and lactate levels (per 1.0 mmol/L increase, OR: 1.127; 95% CI: 1.031-1.232; P = 0.009) were independently associated with high plasma XOR activity (≥ 1,000 pmol/hour/mL). Kaplan-Meier curve analysis indicated that the prognosis, including all-cause death within 30 days, was significantly poorer in high-XOR patients (XOR ≥ 6,670 pmol/hour/mL) than in the other patients.Plasma XOR activity was extremely high in patients with CPA, especially in OHCA. This would be associated with a high lactate value and expected to eventually lead to adverse outcome in patients with CPA.

DOI： 10.1536/ihj.22-584

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The time-dependent changes in the simultaneous evaluation of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels during hospitalization for acute heart failure (AHF) remain obscure.A total of 356 AHF patients were analyzed. Blood samples were collected within 15 minutes of admission (Day 1), 48-120 hours (Day 2-5) and between days 7 and 21 (Before-discharge). Plasma BNP and serum NT-proBNP were significantly decreased on Days 2-5 and Before-discharge in comparison to Day 1, but the NT-proBNP/BNP ratio was not changed. Patients were divided into 2 groups according to the median NT-proBNP/BNP (N/B) ratio on Day 2-5 (Low-N/B versus High-N/B). A multivariate logistic regression model showed that age (per 1-year increase), serum creatinine (per 1.0-mg/dL increase), and serum albumin (per 1.0-mg/dL decrease) were independently associated with High-N/B (odds ratio [OR]: 1.071, 95%confidence interval [CI]: 1.036-1.108, OR: 1.190, 95%CI: 1.121-1.264 and OR: 2.410, 95%CI: 1.121-5.155, respectively). Kaplan-Meier curve analysis showed that the High-N/B group had a significantly poorer prognosis than the Low-N/B group, and a multivariate Cox regression model revealed that High-N/B was an independent predictor of 365-day mortality (hazard ratio [HR]: 1.796, 95%CI: 1.041-3.100) and HF events (HR: 1.509, 95%CI: 1.007-2.263). The same trend in prognostic impact was significantly observed in both low and high delta-BNP cohorts (< 55% and ≥ 55% BNP value on the start date/BNP value at 2-5-days).A high NT-proBNP/BNP ratio on Day 2-5 was associated with non-cardiac conditions and was associated with adverse outcomes even if BNP was adequately decreased by the treatment of AHF.

DOI： 10.1536/ihj.22-350

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：VM Media SP. zo.o VM Group SK  

BACKGROUND: The fibrillatory wave amplitude (FWA) during atrial fibrillation (AF) is thought to reflect structural atrial remodeling, but it remains unclear what determines the FWA. METHODS: 114 consecutive patients were prospectively studied who underwent catheter ablation of AF. The mean FWA was computed by automated surface ECG analyses. The extent of the left atrial (LA) voltage-defined atrial fibrosis and conduction properties were estimated by a three-dimensional high-density electroanatomical mapping system. The LA size was evaluated by transthoracic echocardiography. The study patients were divided into 2 groups according to an FWA in lead V1 above the median value of 46 µV (high FWA group, n=57) or below 46 µV (low FWA group, n=57). RESULTS: There were no differences in the age, gender, CHADS2 score, prevalence of paroxysmal AF, medications, ablation strategy, and LA volume index between the two groups. The LA low voltage areas in the low FWA group were not different from those in the high FWA group. The total LA activation time and local LA conduction velocity did not differ between the two groups. During a median follow-up of 710 days, the recurrence rate after ablation was significantly higher in patients with a low FWA than a high FWA (log-rank P=0.02). In a multivariate analysis, non-paroxysmal AF, the LA volume index, and FWA were independent predictors of recurrence after ablation. CONCLUSIONS: The FWA was not correlated with the markers of atrial structural remodeling. Nevertheless, the FWA could still provide information for predicting the clinical outcome after AF ablation.

DOI： 10.5603/cj.a2022.0120

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Few studies on sudden death (SD) after admission for acute heart failure (AHF) have been published. A total of 1,664 patients with AHF were enrolled in this study, and 1,261 patients who were successfully followed up during the first year after admission were analyzed. The primary end point was SD, which was defined as out-of-hospital cardiac arrest. The median follow-up period from admission was 1,008 days (range 408 to 2,132). In total, 505 patients (40.0%) died: 341 (67.5%) died of cardiovascular causes and 55 (10.9%) died of other causes. Of the 505 who died, 80 (15.8%) experienced SD. The proportion of SDs increased in the later phases of follow-up (0 to 1 year, 10.3%; 1 to 2 years, 18.0%; 2 to 5 years, 18.8%; ≥5 years, 28.2%; p &lt;0.001). A multivariate logistic regression model showed that younger age was independently associated with SD (60 to 69 years: odds ratio 2.249, 95% confidence interval 1.060 to 4.722; &lt;60 years: odds ratio 3.863, 95% confidence interval 1.676 to 8.905). Kaplan-Meier curves showed that the incidence of cardiovascular death was highest during the acute phase, whereas the incidence of SD increased gradually over the entire follow-up period. In conclusion, the incidence of SD was surprisingly high in patients with AHF, accounting for 16% of long-term mortality. The proportion of SDs increased during the very late follow-up phases.

DOI： 10.1016/j.amjcard.2022.05.024

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記述言語：英語  

BACKGROUND: Type-A acute aortic dissection (AAD) with acute coronary involvement can be instantly fatal. The patient's haemodynamics can easily collapse, so rapid decisions regarding treatment strategy are essential. CASE SUMMARY: A 76-year-old man requested an ambulance because of sudden back pain and paraplegia. He was admitted to the emergency room with cardiogenic shock due to acute myocardial infarction with ST-segment elevation. Computed tomography angiography revealed a thrombosed AAD from the ascending to the distal aorta after the renal artery bifurcation, suggesting a retrograde DeBakey type IIIb (DeBakey IIIb + r, Stanford type-A) dissection. He suddenly developed ventricular fibrillation with cardiac arrest and haemodynamic collapse. We thus performed percutaneous coronary intervention (PCI) and thoracic endovascular aortic repair under percutaneous cardiopulmonary support (PCPS). Percutaneous cardiopulmonary support and respiratory support were withdrawn 5 and 12 days after admission, respectively. The patient was transferred to the general ward on Day 28; he was eventually discharged to a rehabilitation hospital on Day 60, having recovered completely. CONCLUSION: Immediate decisions regarding treatment strategy are essential. Non-invasive emergent treatment strategies (such as PCI and TEVAR under PCPS) may be options for critically ill patients with type-A AAD.

DOI： 10.1093/ehjcr/ytac344

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: The role of serum type III procollagen peptide (P3P) level in the acute phase of acute heart failure (AHF) requires clarification. We hypothesized that serum P3P level is temporarily higher during the acute phase, reflecting liver dysfunction due to congestion. METHODS AND RESULTS: A total of 800 AHF patients were screened, and data from 643 patients were analysed. Heart failure was diagnosed by the treating physician according to the European Society of Cardiology (ESC) guidelines, and included patients being treated with high-concentration oxygen inhalation (including mechanical support) for orthopnea, inotrope administration, or mechanical support for low blood pressure, and various types of diuretics for peripheral or pulmonary oedema. In all cases, diuretics or vasodilators were administered to treat AHF. The patients were divided into three groups according to their quartile (Q) serum P3P level: low-P3P (Q1, P3P ≤ 0.6 U/mL), mid-P3P (Q2/Q3, 0.6 < P3P <1.2 U/mL), and high-P3P (Q4, P3P ≥ 1.2 U/mL). The plasma volume status (PVS) was calculated using the following formula: ([actual PV - ideal PV]/ideal PV) × 100 (%). The primary endpoint was 365 day mortality. A Kaplan-Meier curve analysis showed that prognoses, including all-cause mortality and heart failure events within 365 days, were significantly (P < 0.001) worse in the high-P3P group when compared with the mid-P3P and low-P3P groups. A multivariate logistic regression analysis showed that high PVS (Q4, odds ratio [OR]: 4.702, 95% CI: 2.012-20.989, P < 0.001), high fibrosis-4 index (Q4, OR: 2.627, 95% CI: 1.311-5.261, P = 0.006), and low estimated glomerular filtration rate per 10 mL/min/1.73 m2 decrease (OR: 1.996, 95% CI: 1.718-2.326, P < 0.001) were associated with high P3P values. The Kaplan-Meier curve analysis demonstrated a significantly lower survival rate, as well as a higher rate of heart failure events, in the high-P3P and high-PVS groups when compared with the other groups. A multivariate Cox regression model identified high P3P level and high PVS as an independent predictor of 365 day all-cause mortality (hazard ratio [HR]: 2.249; 95% CI: 1.081-3.356; P = 0.026) and heart failure events (HR: 1.586, 95% CI: 1.005-2.503, P = 0.048). CONCLUSION: A high P3P level during the acute phase of AHF served as a comprehensive biomarker of liver dysfunction with volume overload (i.e. liver congestion) and renal dysfunction. A high P3P level at admission may be able to predict adverse outcomes in AHF patients.

DOI： 10.1002/ehf2.13878

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Helicopter emergency medical service (HEMS) has the potential to improve prognosis for acute coronary syndrome (ACS). However, adequacy and effectiveness of HEMS have not been fully evaluated. A total of 862 ACS patients transferred by emergency medical services were divided into two groups: patients transferred by HEMS (n = 171) or by ground ambulance (GA; n = 691). Among them, angiography images for 718 patients (149 in HEMS and 569 in GA group) and optical coherence tomography (OCT) images for 374 patients (75 in HEMS and 299 in GA groups) were analyzed. Additional analysis to compare 2-year cardiac mortality between groups was conducted following propensity score matching to adjust for inter-group differences. ST-segment elevation myocardial infarction (81% vs. 66%, p < 0.001) and cardiogenic shock (Killip IV; 20% vs. 10%, p < 0.001) at admission were more prevalent in HEMS than GA group. Time from admission to balloon angioplasty was shorter in HEMS group (median 54 min vs. 69 min, p < 0.001). Antegrade coronary flow was worse in HEMS group (TIMI flow grade 0 or 1; 68% vs. 51%, p < 0.001). Plaque rupture was more frequently detected by OCT in HEMS group (68% vs. 49%, p = 0.029). Following propensity score matching, the incidence of cardiac death was significantly lower in HEMS group (6.3% vs. 14.9%, p = 0.019). In conclusion, severe ACS patients requiring early reperfusion were appropriately triaged and transferred more rapidly by HEMS. Lower mortality in HEMS group after propensity score matching suggests that HEMS may improve cardiac mortality in ACS patients.

DOI： 10.1007/s00380-022-02022-1

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記述言語：英語  

Thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal insufficiency, and organomegaly (TAFRO) syndrome is treated using corticosteroids and/or immunosuppressive agents as first-line therapy. We report the case of a 69-year-old female with TAFRO syndrome in which the patient presented multiple organ failure and steroid resistance, which was successfully treated using plasma exchange (PE) followed by rituximab. Decisions regarding the next treatment, including PE, are urgent for patients with steroid-resistant TAFRO syndrome. Since it is considered that immunosuppressive agents may be removed by PE, the performance of PE before treatment with immunosuppressive agents might be an option for steroid-resistant TAFRO syndrome.

DOI： 10.14740/jmc3784

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11909/j.issn.1671-5411.2021.10.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Low-triiodothyronine (T3) syndrome is a known complication in intensive care unit (ICU) patients, but the underlying mechanisms and prognostic impact are unclear. Methods and Results: This study retrospectively enrolled 2,976 patients who required care in the ICU. Of these patients, 2,425 were euthyroid and were divided into normal (n=1,666; free T3 [FT3] ≥1.88 µIU/L) and low-FT3 (n=759; FT3 <1.88 µIU/L) groups. Multivariate logistic regression analysis revealed that prognostic nutritional index >46.03 (odds ratio [OR] 2.392; 95% confidence interval [CI] 1.904-3.005), age (per 1-year increase; OR 1.022; 95% CI 1.013-1.031), creatinine (per 0.1-mg/dL increase; OR 1.019; 95% CI 1.014-1.024), and C-reactive protein (per 1-mg/dL increase; OR 1.123; 95% CI 1.095-1.151) were independently associated with low FT3. Survival rates (within 365 days) were significantly lower in the low-FT3 group. A multivariate Cox regression model showed that low FT3 was an independent predictor of 365-day mortality (hazard ratio 1.785; 95% CI 1.387-2.297). Low-T3 syndrome was significantly more frequent in patients with non-cardiovascular than cardiovascular diseases (73.5% vs. 25.8%). Prognosis was significantly poorer in the low-FT3 than normal group for patients with cardiovascular disease, particularly those with acute coronary syndrome and acute heart failure. Conclusions: Low-T3 syndrome was associated with aging, inflammatory reaction, malnutrition, and renal insufficiency and could lead to adverse outcomes in patients admitted to a non-surgical ICU.

DOI： 10.1253/circrep.CR-21-0040

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: The aim of the present study was to consider whether the ultrastructural features of cardiomyocytes in dilated cardiomyopathy can be used to guide genetic testing. METHODS AND RESULTS: Endomyocardial biopsy and whole-exome sequencing were performed in 32 consecutive sporadic dilated cardiomyopathy patients [51.0 (40.0-64.0) years, 75% men] in initial phases of decompensated heart failure. The predicted pathogenicity of ultrarare (minor allele frequency ≤0.0005), non-synonymous variants was determined using the American College of Medical Genetics guidelines. Focusing on 75 cardiomyopathy-susceptibility and 41 arrhythmia-susceptibility genes, we identified 404 gene variants, of which 15 were considered pathogenic or likely pathogenic in 14 patients (44% of 32). There were five sarcomeric gene variants (29% of 17 variants) found in five patients (16% of 32), involving a variant of MYBPC3 and four variants of TTN. A patient with an MYBPC3 variant showed disorganized sarcomeres, three patients with TTN variants located in the region encoding the A-band domain showed sparse sarcomeres, and a patient with a TTN variant in encoding the I-band domain showed disrupted sarcomeres. The distribution of diffuse myofilament lysis depended on the causal genes; three patients with the same TMEM43 variant had diffuse myofilament lysis near nuclei (P = 0.011), while two patients with different DSP variants had lysis in the peripheral areas of cardiomyocytes (P = 0.033). CONCLUSIONS: Derangement patterns of myofilament and subcellular distribution of myofilament lysis might implicate causal genes. Large-scale studies are required to confirm whether these ultrastructural findings are related to the causative genes.

DOI： 10.1002/ehf2.13596

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mechanisms behind poorer cardiac outcomes in underweight patients with acute coronary syndrome (ACS) are not understood and features of coronary culprit lesions in underweight ACS patients have not been fully examined. A total of 1,683 patients with ACS were divided into 4 groups according to body mass index (BMI): <18.5 (n = 73), 18.5 to 24.9 (n = 995), 25 to 29.9 (n = 488), and ≥30 (n = 117). Angiography and optical coherence tomography (OCT) images were analyzed for 1,428 of these patients who had primary percutaneous coronary intervention (PCI) and 838 who had primary PCI with OCT guidance, respectively. Diabetes (p <0.001), hypertension (p <0.001), and dyslipidemia (p <0.001) were less prevalent in BMI <18.5. Statin prescription at discharge was less frequent in the BMI <18.5 group (p <0.001). Quantitative coronary angiography analyses revealed smaller reference vessel (p = 0.001) and minimum lumen diameters after PCI (p = 0.019) and OCT revealed longer lipidic plaque length (p = 0.029) in the BMI <18.5 group. Kaplan-Meier analyses revealed higher rates of cardiac mortality (p <0.001) and major bleeding (p = 0.034) during the 2-year follow-up in the BMI <18.5 group. After adjusting for traditional cardiovascular risk factors, BMI <18.5 independently predicted 2-year cardiac mortality (hazard ratio 1.917 [95% confidence interval [1.082 to 3.397], p = 0.026). In conclusion, being underweight contributed to poorer cardiac outcomes in established ACS population. Smaller minimum lumen diameter after PCI and further progressed atherosclerosis at the culprit lesions despite their lower prevalence of comorbid metabolic risk factors may be related partly to poorer cardiac outcomes.

DOI： 10.1016/j.amjcard.2021.07.041

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記述言語：英語  

DOI： 10.1093/ehjacc/zuab068

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 (SGLT2) inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction (AMI). METHODS: EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with AMI and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis (BIA) were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after AMI onset. We investigated the time course of body fluid balance measured using the BIA device, "InBody®." Primary endpoints were changes in body fluid balance from weeks 0 to 24. RESULTS: Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (p=0.127) and +0.40 L (p=0.001) in ECW [p=0.001], and -0.23 L (p=0.264) and +0.74 L (p<0.001) in ICW [p<0.001], respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with body mass index ≥25 but not in those with <25 kg/m2. CONCLUSIONS: Early SGLT2 inhibitor administration may attenuate changes in ECW and ICW.

DOI： 10.1016/j.cardfail.2021.07.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been recently evaluated as a prognostic marker in patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether a sodium-glucose cotransporter 2 (SGLT2) inhibitor affects the alleviation of heart failure and improvement of PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). METHODS: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of an SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. In total, 105 patients were randomized (1:1) to receive 10 mg empagliflozin or a placebo (once daily), 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS at baseline and weeks 4, 12, and 24. RESULTS: Overall, 96 patients were included in the subgroup analysis set (age 64.3 ± 10.9 years, 80.2% men; 46 in the empagliflozin group and 50 in the placebo group). Body weight and PVS decreased in the empagliflozin group compared with the placebo group at 24 weeks (- 2.2 vs. + 0.1 kg, P < 0.001, and - 5.1 vs. - 0.3%, P < 0.001, respectively). Decreased PVS, defined as a change in PVS of < - 4.5%, was associated with the administration of empagliflozin (odds ratio 2.61, 95% confidence interval 1.11-6.15, P = 0.028). N-terminal pro b-type natriuretic peptide levels decreased in both the empagliflozin and placebo groups (1028.7-370.3 pg/mL, P < 0.001, and 1270.6-673.7 pg/mL, P < 0.01, respectively). CONCLUSION: Empagliflozin reduced the body weight and PVS. Early SGLT2 inhibitor administration in patients with AMI, CHF, and T2DM can therefore be effective in reducing the body weight and PVS. TRIAL REGISTRATION: UMIN 000030158.

DOI： 10.1007/s13300-021-01103-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Fibrosis-4 (FIB4) index could indicate the liver fibrosis in patients with chronic hepatic diseases. It was calculated using the following formula: (age × aspartate aminotransferase [U/L]) / (platelet count [103/μL] × √alanine aminotransferase [U/L]). However, the clinical impact of the FIB4 index in the acute phase of acute heart failure (AHF) has not been sufficiently investigated.A total 1,468 AHF patients were analyzed. The median FIB4 index was 2.71 [1.85-4.22]. The patients were divided into three groups according to the quartiles of their FIB4 index (low-FIB4 [Q1, ≤ 1.847], middle-FIB4 [Q2/Q3, 1.848-4.216], and high-FIB4 [Q4, ≥ 4.216] groups). A Kaplan-Meier curve analysis showed that the prognosis, such as all-cause mortality and HF events within 365 days, was significantly poorer in the high-FIB4 group than in the middle-FIB4 and low-FIB4 groups. A multivariate Cox regression model identified high FIB4 index as an independent predictor of 365-day all-cause death (hazard ratio (HR): 1.660, 95% CI: 1.136-2.427) and HF events (HR: 1.505, 95% CI: 1.145-1.978). The multivariate logistic regression analysis showed that the high plasma volume status (PVS) (Q4, odds ratio [OR]: 2.099, 95% CI: 1.429-3.082), low systolic blood pressure (SBP) (< 100 mmHg, OR: 3.825, 95% CI: 2.504-5.840), and low left ventricular ejection fraction (< 40%, OR: 1.321, 95% CI: 1.002-1.741) were associated with a high FIB4 index.A high FIB4 index can predict adverse outcomes in AHF patients, which indicate that congestive liver and liver hypoperfusion occur due to low cardiac output in the acute phase of AHF.

DOI： 10.1536/ihj.20-793

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Although the reno-protective effects of sodium-glucose cotransporter 2 inhibitors are known in patients with heart failure or type 2 diabetes mellitus (T2DM), this effect has not been confirmed in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The prospective, multicentre, randomized, double-blind, placebo-controlled EMBODY trial investigated patients with AMI and T2DM in Japan. The eligible patients included adults aged 20 years or older, diagnosed with AMI and T2DM, and who could be discharged within 2-12 weeks after the onset of AMI. One hundred and five patients were randomized (1:1) to receive once daily 10 mg empagliflozin or placebo within 2 weeks of AMI onset. In this sub-analysis, we investigated the time course of renal functional parameters such as serum creatinine levels and estimated glomerular filtration rate (eGFR) from baseline to Weeks 4, 12, and 24. Ninety-six patients (64 ± 11 years, 78 male) were included in the full analysis (n = 46 and 50 in the empagliflozin and placebo groups, respectively). We used serum creatinine and eGFR as indicators of renal function. In the placebo group, eGFR decreased from 66.14 mL/min/1.73 m2 at baseline to 62.77 mL/min/1.73 m2 by Week 24 (P = 0.023) but remained unchanged in the empagliflozin group (from 64.60 to 64.36 mL/min/1.73 m2 , P = 0.843). In the latter group, uric acid improved from 5.8 mg/dL at baseline to 4.9 mg/dL at Week 24 (P < 0.001). In the earlier analysis of 56 patients with eGFR ≥ 60 mL/min/1.73 m2 , the eGFR decreased and the serum creatinine increased from baseline to 24 weeks in the placebo group, significantly different to the empagliflozin group (-6.61 vs. +0.22 mL/min/1.73 m2 , P = 0.008 and +0.063 vs. -0.001 mg/dL, P = 0.030, respectively). The changes in serum creatinine and eGFR from baseline to Week 24 were significantly correlated with those in uric acid in the placebo group (r = 0.664, P < 0.001 and r = -0.675, P < 0.001, respectively) but not in the empagliflozin group. CONCLUSIONS: Empagliflozin prevented the kidney functional decline in patients with AMI and T2DM, especially those with baseline eGFR ≥ 60 mL/min/1.73 m2 . Early administration of sodium-glucose cotransporter 2 inhibitors in these patients is considered desirable for renal protection.

DOI： 10.1002/ehf2.13509

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta-blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio-selective beta-blocker use on the long-term outcomes of patients with HF and COPD. METHODS AND RESULTS: Among the 5232 patients with HFrEF (left ventricular ejection fraction of <40%) prospectively enrolled from 11 Asian regions in the ASIAN-HF registry, 412 (7.9%) had a history of COPD. We compared the clinical characteristics and long-term outcomes of the patients with HF and COPD according to the use and type of beta-blockers used: cardio-selective beta-blockers (n = 149) vs. non-cardio-selective beta-blockers (n = 124) vs. no beta-blockers (n = 139). The heart rate was higher, and the outcome was poorer in the no beta-blocker group than in the beta-blocker groups. The 2 year all-cause mortality was significantly lower in the non-cardio-selective beta-blocker group than in the no beta-blocker group. Further, the cardiovascular mortality significantly decreased in the non-cardio-selective beta-blocker group before (hazard ratio: 0.36; 95% confidence interval: 0.18-0.73; P = 0.004) and after adjustments (hazard ratio: 0.37; 95% confidence interval: 0.19-0.73; P = 0.005), but not in the cardio-selective beta-blocker group. CONCLUSIONS: Beta-blockers reduced the all-cause mortality of patients with HFrEF and COPD after adjusting for age and heart rate, although the possibility of selection bias could not be completely excluded due to multinational prospective registry.

DOI： 10.1002/ehf2.13489

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circrep.CR-21-0048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Ongoing myocardial damage at the acme of the sepsis status has not been sufficiently evaluated. The clinical data of 160 sepsis patients who require intensive care and 127 outpatients with chronic heart failure (HF) were compared as a retrospective cohort study. Thereafter, the sepsis patients were divided into 3 groups according to the serum heart-type fatty acid-binding protein (H-FABP) quartiles [low H-FABP = Q1 (n = 39), middle H-FABP = Q2/Q3 (n = 81), and high H-FABP = Q4 group (n = 40)]. The H-FABP level was measured within 15 min of admission. The serum H-FABP levels in the sepsis patients [26.6 (9.3-79.0) ng/ml] were significantly higher than in the choric HF patients [6.6 (4.6-9.7) ng/ml]. A Kaplan-Meier curve showed that the survival rate of the high-H-FABP group was significantly lower than that of the middle- and low-H-FABP groups. The multivariate Cox regression analysis for the 365-day mortality showed that the high-H-FABP group (hazard ratio: 6.544, 95% confidence interval [CI] 2.026-21.140; p = 0.002) was an independent predictor of the 365-day mortality. The same trend in the prognostic impact was significantly (p = 0.015) observed in the cohort that had not been suffering from the cardiac disease before admission. The serum H-FABP level was an independent predictor of the 365-day mortality in the patients who were emergently hospitalized in the intensive-care unit due to sepsis. Ongoing myocardial damage was detected in the majority of patients with sepsis, suggesting that ongoing myocardial damage might be a candidate predictor of adverse outcomes in sepsis patients.

DOI： 10.1007/s00380-021-01865-4

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記述言語：英語  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

β3-Adrenergic receptor expression is enhanced in the failing heart, but its functional effects are unclear. We tested the hypothesis that a β3-agonist improves left ventricular (LV) performance in heart failure. We examined the chronic effects of a β3-agonist in the angiotensin II (Ang II)-induced cardiomyopathy mouse model. C57BL/6J mice were treated with Ang II alone or Ang II + BRL 37344 (β3-agonist, BRL) for 4 weeks. Systolic blood pressure in conscious mice was significantly elevated in Ang II and Ang II + BRL mice compared with control mice. Heart rate was not different among the three groups. Systolic performance parameters that were measured by echocardiography and an LV catheter were similar among the groups. LV end-diastolic pressure and end-diastolic pressure-volume relationships were higher in Ang II mice compared with control mice. However, the increase in these parameters was prevented in Ang II + BRL mice, which suggested improvement in myocardial stiffness by BRL. Pathologic analysis showed that LV hypertrophy was induced in Ang II mice and failed to be prevented by BRL. However, increased collagen I/III synthesis, cardiac fibrosis, and lung congestion observed in Ang II mice were inhibited by BRL treatment. The cardioprotective benefits of BRL were associated with downregulation of transforming growth factor-β1 expression and phosphorylated-Smad2/3. Chronic infusion of a β3-agonist has a beneficial effect on LV diastolic function independent of blood pressure in the Ang II-induced cardiomyopathy mouse model. SIGNIFICANCE STATEMENT: Chronic infusion of a β3-adrenergic receptor agonist attenuates cardiac fibrosis and improves diastolic dysfunction independently of blood pressure in an angiotensin II-induced hypertensive mouse model. This drug might be an effective treatment of heart failure with preserved ejection fraction.

DOI： 10.1124/jpet.120.000140

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記述言語：英語  

J-GLOBAL

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記述言語：英語  

J-GLOBAL

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: The aim of present study is to evaluate the clinical significance of the time-dependent changes in xanthine oxidoreductase (XOR) activity during hospitalization for acute heart failure (AHF). METHODS AND RESULTS: A total of 229 AHF patients who visited to emergency room were prospectively enrolled, and 187 patients were analysed. Blood samples were collected within 15 min of admission (Day 1), after 48-72 h (Day 3), and between Days 7 and 21 (Day 14). The AHF patients were divided into two groups according to the XOR activity on Day 1: the high-XOR group (≥100 pmol/h/mL, n = 85) and the low-XOR group (<100 pmol/h/mL, n = 102). The high-XOR patients were assigned to two groups according to the rate of change in XOR from Day 1 to Day 14: the decreased group (≥50% decrease; n = 70) and the non-decreased group (<50% decrease; n = 15). The plasma XOR activity significantly decreased on Days 3 and 14 [23.6 (9.1 to 63.1) pmol/h/mL and 32.5 (10.2 to 87.8) pmol/h/mL, respectively] in comparison with Day 1 [78.5 (16.9 to 340.5) pmol/h/mL]. A Kaplan-Meier curve indicated that the prognosis, including heart failure (HF) events (all-cause death and readmission by HF) within 365 days, was significantly poorer in the low-XOR patients than in the high-XOR patients and was also significantly poorer in the non-decreased group than in the decreased group. CONCLUSIONS: The plasma XOR activity was rapidly decreased by the appropriate treatment of AHF. Although high-XOR activity on admission was not associated with increased HF events in AHF, high-XOR activity that was not sufficiently reduced during appropriate treatment was associated with increased HF events.

DOI： 10.1002/ehf2.13129

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Given the high prevalence of heart failure (HF) in the elderly, it is essential to establish medical coordination between general practitioners (GPs) and acute care hospitals (ACHs) in an aging society. The aim of this study was to elucidate the status of acceptance of elderly patients with HF and their management requirements in a comprehensive community health system. Furthermore, we investigated GPs' interest in using information and communications technology (ICT) in patient care. Methods and Results: We sent a questionnaire survey to 1,800 GPs in January 2015 and received 392 replies. The overall prevalence of home visits was 55%, with no differences according to GP background characteristics or geographic area. However, less than half (44%) reported accepting patients with symptomatic HF for treatment in their clinic. In addition, only 3 GPs reported accepting and providing emergency visits for patients with refractory HF. In particular, GPs who were not certificated cardiologists, female, and older showed poorer acceptance of symptomatic HF patients. More than half the GPs wanted the prompt acceptance by ACHs of emergency patients, followed by strengthening of home care support at discharge and support for end-of-life care. Half the GPs were interested in telemedicine. Conclusions: ACHs must promptly accept patients with HF in cases of emergency and strengthen nursing care support at discharge. It is also necessary to consider how to support older and female GPs.

DOI： 10.1253/circrep.CR-20-0132

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Various optimal medical therapies have been established for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF). Like HFrEF, HF with a preserved ejection fraction (HFpEF) too is related to poor prognoses. We aimed to investigate the effect of topiroxostat, an oral xanthine oxidoreductase inhibitor, in HFpEF patients with hyperuricemia or gout. METHODS: In this non-randomized, open-label, single-arm trial, we administered topiroxostat (40-160 mg/day) to HFpEF patients with hyperuricemia or gout to achieve a target uric acid level of 6.0 mg/dl. The primary outcome was the rate of change in the log-transformed brain natriuretic peptide (BNP) levels from the baseline to 24 weeks after topiroxostat treatment. The secondary outcomes included the amount of change in the BNP levels, uric acid evaluation values, and oxidative stress marker levels after 24 weeks of topiroxostat treatment. Thirty-six patients were enrolled; three were excluded before study initiation. RESULTS: The log-transformed BNP levels decreased by -3.4 ± 8.9 % (p = 0.043) after 24 weeks of topiroxostat treatment. The rate of change in the BNP level decreased (-18.0 [-57.7, 4.0] pg/ml, p = 0.041). The levels of uric acid and 8-hydroxy-2'-deoxyguanosine/creatinine, an oxidative stress marker, also significantly decreased (-2.8 ± 1.6 mg/dl, p < 0.001, -2.3 ± 3.7 ng/mgCr, p = 0.009, respectively). CONCLUSIONS: The BNP levels were significantly lowered in HFpEF patients with hyperuricemia or gout after topiroxostat administration; however, the rate of decrease was low. Further trials are needed to confirm our findings.

DOI： 10.1272/jnms.JNMS.2021_88-518

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.numecd.2020.09.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prognostic impact of transfer to another hospital among acute heart failure (AHF) patients has not been well elucidated.Of the 800 AHF patients analyzed, 682 patients were enrolled in this study for analysis. The subjects were divided into two groups according to their discharge location: discharge home (Group-H, n = 589) or transfer to another hospital for rehabilitation (Group-T, n = 93). The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and heart failure (HF) events (death, readmission-HF), in Group-T than that in Group-H (P < 0.001, respectively). A multivariate Cox regression model showed that Group-T was an independent predictor of 365-day all-cause death (hazard ratio: 2.618, 95% confidence interval [CI]: 1.510-4.538, P = 0.001). The multivariate logistic regression analysis showed that aging (per 1-year-old increase, odds ratio [OR]: 1.056, 95% CI: 1.028-1.085, P < 0.001), female gender (OR: 2.128, 95% CI: 1.287-3.521, P = 0.003), endotracheal intubation during hospitalization (OR: 2.074, 95% CI: 1.093-3.936, P = 0.026), and increased Controlling Nutritional Status score on admission (per 1.0-point increase, OR: 1.247, 95% CI: 1.131-1.475, P < 0.001) were associated with transfer to another hospital after AHF admission. The prognosis, including all-cause death, was determined to be significantly poorer in patients who were transferred to another hospital, as their activities of daily living were noted to lessen before discharge (n = 11) compared to others (n = 82).Elderly AHF patients suffering from malnutrition were difficult to discharge home after AHF admission, and transfer to another hospital only led to adverse outcomes. Appropriate rehabilitation during definitive hospitalization appears necessary for managing elderly patients in the HF pandemic era.

DOI： 10.1536/ihj.21-126

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記述言語：英語  

DOI： 10.1007/s00380-020-01666-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Serum calcium (Ca) concentrations in the acute phase of acute heart failure (AHF) have not been not sufficiently investigated. Methods and Results: This study enrolled 1,291 AHF patients and divided them into 3 groups based on original and corrected Ca concentrations: (1) hypocalcemia (both original and corrected Ca ≤8.7 mg/dL; n=651); (2) pseudo-hypocalcemia (original and corrected Ca ≤8.7 and >8.7 mg/dL, respectively; n=300); and (3) normal/hypercalcemia (both original and corrected Ca >8.7 mg/dL; n=340). AHF patients were also divided into 2 groups based on corrected Ca concentrations: (1) corrected hypocalcemia (corrected Ca ≤8.7 mg/dL; n=651); and (2) corrected normal/hypercalcemia (corrected Ca >8.7 mg/dL; n=640). Of the 951 patients with original hypocalcemia (≤8.7 mg/dL), 300 (31.5%) were classified as corrected normal/hypercalcemia after correction of Ca concentrations by serum albumin. The prognoses in the pseudo-hypocalcemia, low albumin, and corrected normal/hypercalcemia groups, including all-cause death within 730 days, were significantly poorer than in the other groups. Multivariate Cox regression analysis showed that classification into the pseudo-hypocalcemia, hypoalbumin, and corrected normal/hypercalcemia groups independently predicted 730-day all-cause death (hazard ratios [95% confidence intervals] of 1.497 [1.153-1.943], 2.392 [1.664-3.437], and 1.294 [1.009-1.659], respectively). Conclusions: Corrected normal/hypercalcemia was an independent predictor of prognosis because this group included patients with pseudo-hypocalcemia, which was affected by the serum albumin concentration.

DOI： 10.1253/circrep.CR-20-0068

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4244/EIJ-D-20-00996

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. METHODS AND RESULTS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (1) patients aged 20 years or older and (2) those with left ventricular ejection fraction of ≤ 40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group (hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855). In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure (HF) within 6 months was 0.55 (95% CI: 0.213 to 1.434). The safety profile for eplerenone was as expected. CONCLUSION: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

DOI： 10.1093/ehjcvp/pvaa132

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium-glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency-to-high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT. RESULTS: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was - 0.57 and - 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed. CONCLUSIONS: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. TRIAL REGISTRATION: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442 .

DOI： 10.1186/s12933-020-01127-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circrep.CR-20-0041

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記述言語：英語  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/jaha.119.012199

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記述言語：英語  

DOI： 10.1007/s00380-020-01608-x

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記述言語：英語  

DOI： 10.1253/circrep.CR-19-0116

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DOI： 10.1159/000508037

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DOI： 10.1253/circrep.CR-19-0132

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記述言語：英語  

DOI： 10.1007/s00380-019-01525-8

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記述言語：英語  

DOI： 10.1536/ihj.19-523

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

BACKGROUND: Although heart failure (HF) with preserved ejection fraction (HFpEF) is more common in postmenopausal women than in men, the effect of sex hormones on cardiac diastolic function remains unclear. We examined the effect of gonadectomy with or without the angiotensin receptor blocker olmesartan (Olm) in an isoproterenol (ISO) -induced mouse model of left ventricular hypertrophy (LVH) and cardiac diastolic dysfunction. METHODS: ISO or ISO with Olm were administered for 28 days in sham-operated male and female, castrated (CAS), and ovariectomized (OVX) mice. LV ejection fraction (EF) and E/A ratio were analyzed by echocardiography, and the LV and lung weight corrected by tibial length were used as indices of LVH and lung congestion, respectively. RESULTS: On echocardiography, systolic function did not differ between the four groups. LV/tibial length (TL) and Lung/TL significantly increased in all groups. The LV/TL ratio was lower in castrated-ISO vs. Male-Sham-ISO but did not differ between Female-Sham-ISO and OVX-ISO. However, the Lung/TL ratio of OVX-ISO was greater than that of Female-Sham-ISO. Olm prevented LV hypertrophy in all groups. The decrease in E/A and increase in lung weight were improved by Olm in Male-Sham and OVX-ISO but not in the other groups. CONCLUSION: These sex differences suggest that sex hormones play a pivotal role in modulating cardiac hypertrophy and diastolic dysfunction induced by chronic β-adrenoceptor stimulation, and thus affect the therapeutic potential of angiotensin receptor blockade.

DOI： 10.1272/jnms.jnms.2021_88-303

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記述言語：英語  

DOI： 10.1177/2048872618822473

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記述言語：英語  

DOI： 10.1016/j.ijcard.2019.09.020

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担当区分：筆頭著者   記述言語：英語  

DOI： 10.1016/j.amjcard.2019.10.051

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記述言語：英語  

DOI： 10.1016/j.ijcard.2019.08.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Plasma volume status (PVS) has been evaluated recently as a prognostic marker of acute heart failure (AHF). However, whether evaluating PVS alone is sufficient remains unclear. Methods: Of 675 patients with AHF screened, 601 were enrolled. The PVS, prognostic nutritional index (PNI) (lower = worse), and Controlling Nutritional Status (CONUT) score (higher = worse) were evaluated. Patients were divided into 2 groups according to PVS value (low- or high-PVS group) and were further subdivided into 4 groups (low- or high-PVS/CONUT group and low- or high-PVS/PNI group). Results: A Kaplan-Meier curve showed a significantly lower survival rate in the high-PVS group than in the low-PVS group, the high-PVS/high-CONUT group than in the high-PVS/low-CONUT group, and the high-PVS/low-PNI group than in the high-PVS/high-PNI group. A multivariate Cox regression model showed that high PVS (hazard ratio [HR], 1.642; 95% confidence interval [CI], 1.049-2.570) and high PVS/high CONUT (HR, 2.076; 95% CI, 1.147-3.757) and high PVS/low PNI (HR, 2.094; 95% CI, 1.166-3.761) were independent predictors of 365-day mortality. Conclusions: An adverse outcome was predicted by the evaluation of PVS; furthermore, a malnutrition status with a high PVS leads to an adverse outcome. The simultaneous evaluation of nutrition status and PVS is essential to predict an AHF outcome.

DOI： 10.1016/j.cjco.2019.10.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective The aim of present study was to elucidate the gender differences in social determinants among patients with acute heart failure (AHF). Methods A total of 1,048 AHF patients were enrolled, and the 508 AHF patients who were ≥75 years old and the 540 patients who were <75 years old were evaluated as the elderly and non-elderly cohorts, respectively. Participants who met one of the three marital status-, offspring-, and living status-related criteria were considered socially vulnerable, and subjects were thus classified into socially vulnerable and non-socially vulnerable groups by gender in both the non-elderly and elderly cohorts. Social vulnerability was significantly more common in the elderly cohort (n=246, 48.4%) than in the non-elderly cohort (n=197, 36.5%) and significantly more common in the elderly women (n=157, 69.4%) than in the elderly men (n=89, 31.5%). Kaplan-Meier curves showed that the survival rate of the socially vulnerable group was significantly poorer than that of the non-socially vulnerable group in the elderly male cohort (p=0.010). Social vulnerability was an independent predictor of the 1,000-day mortality in the elderly male cohort (hazard ratio: 1.942, 95% confidence interval: 1.102-3.422) but not in the elderly female cohort according to a multivariate analysis. Conclusion Social vulnerability was shown to be more common in elderly female AHF patients than in elderly men, although it was associated with a poor prognosis in elderly men. Reinforcing the social structure of elderly male AHF patients might help improve their prognosis.

DOI： 10.2169/internalmedicine.2757-19

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

Background: Although the obesity paradox may vary depending upon clinical background factors such as age, gender, aetiology of heart failure and comorbidities, the reasons underlying the heterogeneous impact of body mass index (BMI) on in-hospital cardiac mortality under various conditions in patients with acute heart failure syndromes (AHFSs) remain unclear. Methods: Among 4617 hospitalised patients with AHFSs enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, the patient characteristics and in-hospital cardiac mortality rates in those with low BMI (BMI <25 kg/m(2), n = 3263) were compared to those with high BMI (BMI > 25 kg/m(2), n = 1354). Results: Compared to the high-BMI group, the low-BMI group was significantly older, less likely to be male and to have hypertensive or idiopathic dilated aetiologies and more likely to have valvular aetiologies and a history of prior hospitalisation for AHFS. The low-BMI group also had lower prevalence rates of diabetes, dyslipidaemia, hypertension and atrial fibrillation and higher prevalence rates of anaemia and chronic obstructive pulmonary disease. In addition, cardiac mortality was significantly higher in the low-BMI group than in the high-BMI group (5.5 vs. 1.5%, p < 0.001). Logistic regression analysis demonstrated that low BMI was a predictor of cardiac mortality (odds ratio: 3.89, 95% confidence interval: 2.44-6.21). In subgroup analyses, the impact of BMI on cardiac mortality differed depending on the presence of hypertensive aetiology, hypertension, chronic obstructive pulmonary disease and hyponatremia (all p < 0.05), although there were no interactions between the impacts of BMI and age, gender, other aetiologies, prior hospitalisation, diabetes, anaemia, cardio-renal function and in-hospital management. Conclusion: It is necessary to appreciate the obesity paradox in AHFS patients, and a patient's heterogeneous background should also be considered.

DOI： 10.1177/2048872617703061

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: The importance of true worsening renal failure (WRF), which is associated with a poor prognosis, had been suggested in patients with acute heart failure (AHF). The aim of the present study was to establish the biomarker strategy for the prediction of true WRF in AHF. METHODS AND RESULTS: Two hundred eighty-one patients with AHF were analysed. Their biomarkers were measured within 30 min of admission. Patients were assigned to the non-WRF (n = 168), pseudo-WRF (n = 56), or true-WRF (n = 57) groups using the criteria of both acute kidney injury on admission and increasing serum creatinine value during the first 7 days. A Kaplan-Meier curve showed that the survival and heart failure event rate of the true-WRF group within 1000 days was significantly lower than that of the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate Cox regression model also indicated that true WRF was an independent predictor of 1000 day mortality and heart failure events [hazard ratio: 4.315, 95% confidence interval (CI): 2.466-7.550, P ≤ 0.001, and hazard ratio: 2.834, 95% CI: 1.893-4.243, P ≤ 0.001, respectively]. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the true-WRF group than in the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate logistic regression model indicated that the predictive biomarker for the true-WRF group was the s-HFABP level (odds ratio: 5.472, 95% CI: 2.729-10.972, P ≤ 0.001). The sensitivity and specificity for indicating the presence of true WRF were 73.7% and 76.8% (area under the curve = 0.831) for s-HFABP in whole patients, respectively, and 94.7% and 72.7% (area under the curve = 0.904) in non-chronic kidney disease (CKD) patients, respectively. CONCLUSIONS: Cardiac biomarkers, especially the s-HFABP, might predict the development of true WRF in AHF patients. Furthermore, the predictive value was higher in AHF patients without CKD than in those with CKD.

DOI： 10.1002/ehf2.12414

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Plasma xanthine oxidoreductase (XOR) activity during the acute phase of acute heart failure (AHF) requires further elucidation. METHODS AND RESULTS: One hundred eighteen AHF patients and 231 control patients who attended a cardiovascular outpatient clinic were prospectively analysed. Blood samples were collected within 15 min of admission from AHF patients (AHF group) and control patients who visited a daily cardiovascular outpatient clinic (control group). Plasma XOR activity was compared between the two groups, and factors independently associated with extremely elevated XOR activity were identified using a multivariate logistic regression model. Plasma XOR activity in the AHF group (median, 104.0 pmol/h/mL; range, 25.9-423.5 pmol/h/mL) was significantly higher than that in the control group (median, 45.2 pmol/h/mL; range, 19.3-98.8 pmol/h/mL). The multivariate logistic regression model showed that serum uric acid (per 1.0 mg/dL increase, odds ratio: 1.280; 95% confidence interval: 1.066-1.536; P = 0.008) and lactate levels (per 1.0 mmol/L increase, odds ratio: 1.239; 95% confidence interval: 1.040-1.475; P = 0.016) were independently associated with high plasma XOR activity (>300 pg/h/mL) during the acute phase of AHF. CONCLUSIONS: Plasma XOR activity was extremely high in patients with severely decompensated AHF. This would be associated with a high lactate value and would eventually lead to hyperuricaemia in patients with AHF.

DOI： 10.1002/ehf2.12390

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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DOI： 10.1016/j.amjcard.2019.06.025

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DOI： 10.1016/j.ijcha.2019.03.005

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DOI： 10.1016/j.amjcard.2019.03.045

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DOI： 10.1159/000496053

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記述言語：英語  

DOI： 10.1007/s00380-019-01347-8

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DOI： 10.1253/circrep.CJ-18-0014

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DOI： 10.2463/mrms.mp.2017-0136

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Protection from lethal ventricular arrhythmias leading to sudden cardiac death is one of the most important problems after myocardial infarction. Cardiac sympathetic hyperactivity is related to poor prognosis and fatal arrhythmias and can be non-invasively assessed with heart rate variability, heart rate turbulence, T-wave alternans, late potentials, and 123I-meta-iodobenzylguanide (123I-MIBG) scintigraphy. Sodium glucose cotransporter 2 (SGLT2) inhibitors potentially reduce sympathetic nervous system activity that is augmented in part due to the stimulatory effect of hyperglycemia. The EMBODY trial is designed to determine whether the suppression of cardiac sympathetic activity induced by the SGLT2 inhibitor is accompanied by protection against adverse cardiovascular outcomes. METHODS: The EMBODY trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with acute MI and type 2 diabetes in Japan. A total of 98 patients will be randomized (1:1) to receive once-daily placebo or empagliflozin, an SGLT2 inhibitor, 10 mg. The primary end point is the change from baseline to 24 weeks in heart rate variability. Secondary end points include the change from baseline for other sudden cardiac death surrogate-markers such as heart rate turbulence, T-wave alternans, late potentials, and 123I-MIBG scintigraphy imaging. Adverse effects will be evaluated throughout the trial period. PLANNED OUTCOMES: The EMBODY trial will evaluate the potential cardioprotective effect of empagliflozin and will provide additional important new data regarding its preventative effects on sudden cardiac death. TRIAL REGISTRATION: Unique Trial Number, UMIN000030158 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034442 ). FUNDING: Nippon Boehringer Ingelheim and Eli Lilly and Company.

DOI： 10.1007/s13300-018-0480-7

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Whether or not the definition of a worsening renal function (WRF) is adequate for the evaluation of acute renal failure in patients with acute heart failure is unclear. METHODS AND RESULTS: One thousand and eighty-three patients with acute heart failure were analysed. A WRF, indicated by a change in serum creatinine ≥0.3 mg/mL during the first 5 days, occurred in 360 patients while no-WRF, indicated by a change <0.3 mg/dL, in 723 patients. Acute kidney injury (AKI) upon admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value and placed into groups based on the degree of AKI: no-AKI (n = 751), Class R (risk; n = 193), Class I (injury; n = 41), or Class F (failure; n = 98). The patients were assigned to another set of four groups: no-WRF/no-AKI (n = 512), no-WRF/AKI (n = 211), WRF/no-AKI (n = 239), and WRF/AKI (n = 121). A multivariate logistic regression model found that no-WRF/AKI and WRF/AKI were independently associated with 365 day mortality (hazard ratio: 1.916; 95% confidence interval: 1.234-2.974 and hazard ratio: 3.622; 95% confidence interval: 2.332-5.624). Kaplan-Meier survival curves showed that the rate of any-cause death during 1 year was significantly poorer in the no-WRF/AKI and WRF/AKI groups than in the WRF/no-AKI and no-WRF/no-AKI groups and in Class I and Class F than in Class R and the no-AKI group. CONCLUSIONS: The presence of AKI on admission, especially Class I and Class F status, is associated with a poor prognosis despite the lack of a WRF within the first 5 days. The prognostic ability of AKI on admission may be superior to WRF within the first 5 days.

DOI： 10.1002/ehf2.12264

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ehf2.12228

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語  

DOI： 10.1016/j.ijcard.2017.09.004

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DOI： 10.1007/s00380-018-1204-7

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DOI： 10.1007/s00380-018-1151-3

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担当区分：責任著者   記述言語：英語  

DOI： 10.1007/s00380-018-1154-0

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DOI： 10.1016/j.jjcc.2018.01.014

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DOI： 10.1007/s00380-017-1053-9

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DOI： 10.1007/s00380-017-1057-5

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DOI： 10.1007/s00380-017-1034-z

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DOI： 10.1016/j.ijcard.2018.07.074

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

Background: The clinical significance of urinary liver fatty acid-binding protein (u-LFABP) in acute heart failure (AHF) patients remains unclear. Methods and Results: The u-LFABP levels on admission of 293 AHF patients were analyzed. The patients were divided into 2 groups according to the u-LFABP quartiles (Q1, Q2, and Q3 = low u-LFABP [L] group vs. Q4 = high u-LFABP [H] group). We evaluated the diagnostic and prognostic value of u-LFABP and compared the findings between the chronic kidney disease (CKD; n = 165) and non-CKD patients (n = 128). Acute kidney injury (AKI) during the first 7 days was evaluated based on the RIFLE criteria. In the non-CKD group, the number of AKI patients during the first 7 days was significantly greater in the H group (70.0%) than in the L group (45.6%). A multivariate logistic regression model indicated that the H group (odds ratio: 3.850, 95% confidence interval [CI] 1.128-13.140) was independently associated with AKI during the first 7 days. The sensitivity and specificity of u-LFABP for predicting AKI were 63.6 and 59.7% (area under the ROC curve 0.631) at 41.9 ng/mg × cre. A Cox regression model identified the H group (hazard ratio: 13.494, 95% CI 1.512-120.415) as an independent predictor of the 60-day mortality. A Kaplan-Meier curve, including all-cause death within 60 days, showed a significantly poorer survival rate in the H group than in the L group (p = 0.036). Conclusions: The u-LFABP level is an effective biomarker for predicting AKI during the first 7 days of hospitalization and an adverse outcome in AHF patients with non-CKD.

DOI： 10.1159/000477825

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掲載種別：研究論文（学術雑誌）  

© 2017 Elsevier Inc. The aim of this study was to evaluate the association of functional mitral regurgitation (FMR), preserved or reduced ejection fraction (EF), and ischemic or nonischemic origin with outcomes in patients discharged alive after hospitalization for acute decompensated heart failure (HF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 3,357 patients were evaluated to assess the association of FMR, preserved or reduced EF, and ischemic or nonischemic origin with the primary end point (all-cause death and readmission for HF after discharge). At the time of discharge, FMR was assessed semiquantitatively (classified as none, mild, or moderate to severe) by color Doppler analysis of the regurgitant jet area. According to multivariable analysis, in the ischemic group, either mild or moderate to severe FMR in patients with a preserved EF had a significantly higher risk of the primary end point than patients without FMR (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.12 to 2.29; p = 0.010 and HR 1.98; 95% CI 1.30 to 3.01; p = 0.001, respectively). In patients with reduced EF with an ischemic origin, only moderate to severe FMR was associated with a significantly higher risk of the primary end point (HR 1.67; 95% CI 1.11 to 2.50; p = 0.014). In the nonischemic group, there was no significant association between FMR and the primary end point in patients with either a preserved or reduced EF. In conclusion, among patients with acute decompensated HF with a preserved or reduced EF, the association of FMR with adverse outcomes may differ between patients who had an ischemic or nonischemic origin of HF.

DOI： 10.1016/j.amjcard.2017.05.051

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.jjcc.2017.02.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with acute heart failure (AHF) commonly have multiple co-morbidities, and some of these patients die in the hospital from causes other than aggravated heart failure. However, limited information is available on the mode of death in patients with AHF. Therefore, the present study was performed to determine the incidence and predictors of in-hospital non-cardiac death in patients with AHF, using the Acute Decompensated Heart Failure Syndromes (ATTEND) registry Methods: The ATTEND registry included 4842 consecutive patients with AHF admitted between April 2007-September 2011. The primary endpoint of the present study was in-hospital non-cardiac death. A stepwise regression model was used to identify the predictors of in-hospital non-cardiac death. RESULTS: The incidence of all-cause in-hospital mortality was 6.4% ( n=312), and the incidence was 1.9% ( n=93) and 4.5% ( n=219) for non-cardiac and cardiac causes, respectively. Old age was associated with in-hospital non-cardiac death, with a 42% increase in the risk per decade (odds 1.42, p=0.004). Additionally, co-morbidities including chronic obstructive pulmonary disease (odds 1.98, p=0.034) and anaemia (odds 1.17 (per 1.0 g/dl decrease), p=0.006) were strongly associated with in-hospital non-cardiac death. Moreover, other predictors included low serum sodium levels (odds 1.05 (per 1.0 mEq/l decrease), p=0.045), high C-reactive protein levels (odds 1.07, p<0.001) and no statin use (odds 0.40, p=0.024). CONCLUSIONS: The incidence of in-hospital non-cardiac death was markedly high in patients with AHF, accounting for 30% of all in-hospital deaths in the ATTEND registry. Thus, the prevention and management of non-cardiac complications are vital to prevent acute-phase mortality in patients with AHF, especially those with predictors of in-hospital non-cardiac death.

DOI： 10.1177/2048872615593388

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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DOI： 10.1007/s00380-016-0893-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

BACKGROUND: The purposes of this study were to assess the usefulness of myocardial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for evaluating myocardial metabolic status in hypertrophic cardiomyopathy (HCM) and the therapeutic efficacy of alcohol septal ablation (ASA) in hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Thirty HCM patients (64.4±10.5 years, 14 male, 12 hypertrophic non-obstructive cardiomyopathy [HNCM], 16 HOCM, and 2 dilated phase of HCM) underwent 18F-FDG-PET/CT. 18F-FDG uptake was semi-quantitatively evaluated using an uptake score in each 17 segment and the entire LV or regional standardized uptake value (SUV). RESULTS: 18F-FDG uptake was observed mostly in a hypertrophied myocardium in HNCM patients, whereas 18F-FDG was extensively accumulated beyond the hypertrophied myocardium in HOCM patients. There was a positive correlation between the summed uptake score of 18F-FDG and high-sensitive troponin T level in HNCM patients (r = 0.603, p = 0.049), whereas the score was positively correlated with brain natriuretic peptide level (r = 0.614, p = 0.011) in HOCM patients. In 10 patients who received ASA, the maximum SUV of the entire LV was significantly reduced from 5.6±2.6 to 3.2±2.1 (p = 0.040) after ASA. Reduction of that maximum SUV was particularly significant in the lateral region (from 5.5±2.6 to 2.9 ±2.2, p = 0.024) but not significant in the anteroseptal region (from 4.5±2.6 to 2.9±1.6, p = 0.12). CONCLUSION: Extensive 18F-FDG uptake beyond the hypertrophied myocardium was observed in HOCM. ASA attenuates 18F-FDG uptake in a remote lateral myocardium.

DOI： 10.1371/journal.pone.0188479

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DOI： 10.2463/mrms.rev.2016-0116

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DOI： 10.1007/s00380-016-0908-9

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DOI： 10.1016/j.amjcard.2017.03.248

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DOI： 10.1016/j.jjcc.2016.11.015

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記述言語：日本語   出版者・発行元：日本心臓血管内視鏡学会  

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記述言語：英語   出版者・発行元：Dr. Dietrich Steinkopff Verlag GmbH and Co. KG  

DOI： 10.1007/s00392-016-0981-1

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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DOI： 10.1186/s12872-016-0340-1

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記述言語：英語  

DOI： 10.1038/hgv.2016.22

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DOI： 10.1016/j.ejim.2015.08.015

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記述言語：英語  

DOI： 10.1155/2016/3749489

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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DOI： 10.1177/0284185115580840

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DOI： 10.1080/15548627.2016.1145326

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担当区分：責任著者   記述言語：英語  

DOI： 10.1016/j.mri.2016.05.008

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/COPD.S101082

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DOI： 10.1016/j.jjcc.2016.04.013

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DOI： 10.1371/journal.pone.0167645

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記述言語：英語   出版者・発行元：Elsevier Inc.  

DOI： 10.1016/j.amjcard.2015.07.004

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DOI： 10.1016/j.amjcard.2015.07.004

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DOI： 10.1007/s00380-013-0461-8

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DOI： 10.1007/s00392-014-0774-3

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2147/COPD.S79942

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DOI： 10.1016/j.amjcard.2015.05.006

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DOI： 10.1016/j.amjcard.2015.06.023

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記述言語：英語  

DOI： 10.1093/eurheartj/ehu404

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DOI： 10.1253/circj.CJ-14-0653

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DOI： 10.1007/s10557-014-6565-2

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DOI： 10.1016/j.jjcc.2014.03.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Ltd  

Background: The efficacy of thrombolytic therapy in patients with submassive pulmonary embolism (PE) remains unclear. Previous meta-analyses have not separately reported the proportion of patients with submassive PE. Objective: We assessed the effect of thrombolytic therapy on mortality, recurrent PE, clinical deterioration requiring treatment escalation and bleeding in patients with submassive PE. Methods: The MEDLINE, EMBASE and Cochrane Library databases were searched to identify all relevant randomized controlled trials comparing adjunctive thrombolytic therapy with heparin alone as initial treatments in patients with acute submassive PE, and reported 30-day mortality or in-hospital clinical outcomes. Results: A total of 1510 patients were enrolled in this meta-analysis. No significant differences were apparent in the composite endpoint of all-cause death or recurrent PE between the adjunctive thrombolytic therapy arm and the heparin-alone arm (3.1% vs. 5.4%
RR, 0.64 [0.32-1.28]
P = 0.2). Adjunctive thrombolytic therapy significantly reduced the incidence of the composite endpoint of all-cause death or clinical deterioration (3.9% vs. 9.4%
RR, 0.44
P &lt
0.001). There were no statistically significant associations for major bleeding when adjunctive thrombolytic therapy was compared with heparin therapy alone (6.6% vs. 1.9%
P = 0.2). Conclusions: This meta-analysis shows that adjunctive thrombolytic therapy does not significantly reduce the risk of mortality or recurrent PE in patients with acute submassive PE, but that adjuvant thrombolytic therapy prevents clinical deterioration requiring the escalation of treatment in patients with acute submassive PE. Bleeding risk assessment might be the most successful approach for improving clinical outcomes and patient-specific benefit. © 2014 International Society on Thrombosis and Haemostasis.

DOI： 10.1111/jth.12608

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DOI： 10.1253/circj.CJ-13-1255

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DOI： 10.1002/cbf.2973

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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DOI： 10.1136/bmjopen-2014-005968

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DOI： 10.1016/j.cardfail.2014.07.278

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DOI： 10.1007/s00392-014-0717-z

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DOI： 10.1007/s00392-014-0748-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/CIRCULATIONAHA.112.000602

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ijcard.2012.09.046

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The aim of the present study was to investigate whether percutaneous coronary intervention-related periprocedural myocardial infarction (MI) can be suppressed more significantly with high- compared with low-dose rosuvastatin. A total of 232 patients scheduled to undergo elective percutaneous coronary intervention within 5 to 7 days were assigned to groups that would receive either 2.5 or 20 mg/day of rosuvastatin (n = 116 each). The incidence of periprocedural MI did not significantly differ between the high and low-dose groups (8.7% vs 18.7%, p = 0.052). In patients who were not taking statins at the time of enrollment, high-dose rosuvastatin significantly suppressed periprocedural MI compared with the low dose (10.5% vs 30.0%, p = 0.037). The difference was not significant in patients who were already taking statins (high vs low dose 7.6% vs 10.6%, p = 0.582). In conclusion, the incidence of percutaneous coronary intervention-related periprocedural MI was reduced more effectively by high-dose than by low-dose rosuvastatin in statin-naive patients. However, low-dose rosuvastatin is sufficient for patients who are already taking statins.

DOI： 10.1016/j.amjcard.2013.02.018

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DOI： 10.1016/j.ijcard.2012.09.046

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DOI： 10.1016/j.ijcard.2013.07.032

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DOI： 10.1272/jnms.80.25

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DOI： 10.1253/circj.CJ-12-1326

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DOI： 10.1016/j.jjcc.2012.10.004

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DOI： 10.1016/j.cardfail.2013.05.009

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DOI： 10.1016/j.amjcard.2012.12.019

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DOI： 10.1253/circj.CJ-12-0994

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DOI： 10.1016/j.amjcard.2013.02.018

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DOI： 10.1253/circj.CJ-13-0187

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DOI： 10.1161/CIRCULATIONAHA.112.000602

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DOI： 10.1016/j.cardfail.2012.08.038

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Heart Journal Association  

A 58-year-old male with a history of prior myocardial infarction, hypertension, and dyslipidemia was admitted due to deteriorating exertional angina. A bare metal stent (Multilink plus™, GUIDANT Corporation, Santa Clara, CA, USA) had been implanted into the proximal left anterior descending artery because of ST-elevation myocardial infarction 7 years earlier. Optical coherence tomography (OCT) showed a disruption of the atherosclerotic neointima overlying the stent. Intravascular imaging studies and pathological studies have shown that neointima within a bare-metal stent often transform into atherosclerotic tissue during an extended period of time. In the current report, OCT demonstrated that a disruption of the atherosclerotic neointima has the potential to cause the development of unstable clinical features. OCT examinations therefore help to understand the pathogenesis of acute coronary syndrome after stent implantation.

DOI： 10.1536/ihj.53.261

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DOI： 10.1016/j.jjcc.2012.06.004

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DOI： 10.1016/j.jjcc.2012.01.009

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DOI： 10.1007/s12928-011-0055-2

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DOI： 10.1016/j.jjcc.2010.10.004

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DOI： 10.1016/j.jjcc.2010.10.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: CHADS2 score can quantify risk of stroke for patients who have atrial fibrillation (AF) and may aid in selection of antithrombotic therapy. The aim of this study was to investigate the relationship between CHADS2 score and antithrombotic therapy in acute decompensated heart failure (ADHF) patients with AF. Methods: The ATTEND registry in an ongoing prospective observational multicenter cohort study of patients hospitalized for ADHF in Japan. We evaluated 1027 ADHF patients with AF admitted to 48 hospitals (mean age 74.8±11.5year old, male 56.2%, LVEF 49.1 ±16.7%). We classified them in 6 groups according to CHADS2 score of 1 to 6 (score1:n=133, 2:n=279, 3:n=366, 4:n=132, 5:n=86, 6:n=31). Antithrombotic therapy was compared according to CHADS2 score. Results: As the CHADS2 score increased, the ratio of warfarin use was decreased (total:77.0%, score1:85.7%, 2:83.5%, 3:73.2%, 4:78.0%, 5:60.5%, 6:67.7%, p&lt
0.001). On the other hand, the ratio of aspirin use was increased (total:35.3%, score1:17.3%, 2:27.6%, 3:41.3%, 4:43.2%, 5:43.0%, 6:58.1%, p&lt
0.001). Conclusion: In ADHF patients with AF, the underuse of warfarin were observed at high CHADS2 score. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.OP49_3

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記述言語：英語  

DOI： 10.1016/j.ijcard.2011.09.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The AngioSculpt scoring balloon catheter (AngioScore, Inc., Fremont, California) has recently been developed for percutaneous intervention in coronary and peripheral arteries. This device is composed of two major components, a minimally compliant balloon and three nitinol wore. The three wires encapsulate the low-compliant balloon in a spiral configuration. The concept is for the spiral wires to score the lumen surface during balloon expansion. However, the precise mechanisms and efficacy of this scoring technology in humans had not yet to be determined. In this case, both a de novo coronary lesion and an in-stent restenosis lesion were treated with the scoring balloon and were subsequently observed via optical coherence tomography (OCT) with high-resolution images ( approximately 15 microm). OCT clearly demonstrated the effects of this device on plaque and neointimal hyperplasia scoring, as well as its ability to achieve sufficient lumen sizes after coronary artery dilatation.

DOI： 10.1016/j.ijcard.2008.11.154

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

DOI： 10.1016/j.ahj.2010.03.019

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記述言語：英語  

DOI： 10.1016/j.jjcc.2010.07.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Plaque disruption, which may be associated with some coronary risk factors, plays a key role in the development of acute coronary syndromes and progression of atherosclerosis. However, the clinical profile of asymptomatic plaque disruption in stable ischemic heart disease has not been well evaluated. The aim of the present study was to investigate the frequency and determinants of silent plaque disruption (SPD) in patients with stable ischemic heart disease using coronary angioscopy. Forty-one patients with stable angina or old myocardial infarction (OMI) without any complaints within 3 months were included in the present study. Angioscopy was successfully performed through 49 nonischemic related coronary arteries. The presence of SPD and coronary risk factors were recorded. Silent plaque disruption was found in 12 patients with stable ischemic heart disease (12/41, 29.3%), and the frequency of SPD in nonischemic related coronary arteries was 26.5% (13/49). A significantly higher frequency of SPD was noted in yellow plaques than in white plaques (35.3% versus 6.7%, P = 0.043). Overall, the independent clinical risk factors of SPD in nonischemic related coronary arteries were diabetes mellitus (P = 0.018; OR, 18.8209; 95% CI, 1.6525 to 214.3523) and hypertension (P = 0.0313; OR, 6.6485; 95% CI, 1.1850 to 37.3019). These results suggest silent plaque disruption was commonly observed in nonischemic related coronary arteries in patients with stable ischemic heart disease and its determinants were diabetes mellitus and hypertension.

DOI： 10.1536/ihj.51.383

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記述言語：英語  

DOI： 10.1536/ihj.51.404

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記述言語：英語  

DOI： 10.1536/ihj.51.383

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記述言語：英語  

DOI： 10.1038/hr.2010.77

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記述言語：英語  

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記述言語：英語  

DOI： 10.1536/ihj.48.1

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記述言語：日本語  

J-GLOBAL

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Experimental study has shown that blunted arterial baroreflex function markedly attenuated inotropic responses to a phosphodiesterase inhibitor (PDEI) even in normal hearts. However, whether arterial baroreflex function is related to the inotropic responsiveness to a PDEI has not been clarified in human heart failure (HF). HYPOTHESIS: The goal of this study was to examine the relationship between inotropic responses to a PDEI and arterial baroreflex sensitivity in human HF. METHODS: Twelve patients with HF were examined, and hemodynamic responses to milrinone (12.5, 25, and 50 microg/kg, intravenous injection) and arterial baroreflex sensitivity were assessed by pulse interval-left ventricular (LV) systolic pressure slope using nitroglycerin and phenylephrine. RESULTS: Milrinone (25 microg/kg) significantly increased LV dP/dt. Arterial baroreflex sensitivity was only one predictor of inotropic responses to milrinone by multivariate analysis; a strong positive correlation was also found between LV dP/dt and baroreflex sensitivity (y = 6.656X - 3.326, r = 0.93, p = 0.000). CONCLUSION: Inotropic effects of milrinone, a PDEI, correlated significantly with arterial baroreflex sensitivity, suggesting that the more baroreflex function was impaired, the more the inotropic effect of a PDEI was depressed in human HF.

DOI： 10.1002/clc.4960290608

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined the effects of gender and aging on cardiac and peripheral hemodynamic responses to beta-adrenergic receptor (beta-AR) stimulation in young (male = 5.9 +/- 0.4 yr old and female = 6.5 +/- 0.7 yr old) and old (male = 19.8 +/- 0.7 yr old and female = 21.2 +/- 0.2 yr old) conscious monkeys (Macaca fascicularis), chronically instrumented for measurements of left ventricular (LV) and arterial pressures as well as cardiac output. Baseline LV pressure, the first derivative of LV pressure (LV dP/dt), cardiac index, mean arterial pressure, total peripheral resistance (TPR), and heart rate in conscious monkeys were not different among the four groups. Increases in LV dP/dt in response to 0.1 microg/kg isoproterenol (Iso) were diminished (P < 0.05) in old males (+99 +/- 11%) compared with young males (+194 +/- 18%). In addition, the inotropic responses to norepinephrine (NE) and forskolin (FSK) were significantly depressed (P < 0.05) in old males. Iso-induced reductions of TPR were less (P < 0.05) in old males (-28 +/- 2%) than in young males (-49 +/- 2%). The changes of TPR in response to NE and FSK were also significantly attenuated (P < 0.05) in old males. However, the LV dP/dt responses to BAY y 5959 (15 microg. kg-1. min-1), a Ca2+ channel promotor independent of beta-AR signaling, were not significantly different between old and young males. In contrast to results in male monkeys, LV dP/dt and TPR responses to Iso, NE, and FSK in old females were similar to those observed in young females. Thus both cardiac contractile and peripheral vascular dynamic responses to beta-AR stimulation are preserved in old female but not old male monkeys. This may explain, in part, the reduced cardiovascular risk in the older female population.

DOI： 10.1152/ajpheart.01034.2002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To seek evidence that the nonhuman primate arterial wall, as it ages in the absence of atherosclerosis, exhibits alterations in pathways that are involved in the pathogenesis of experimental atherosclerosis, we assessed aortic matrix metalloproteinase-2 (MMP-2) and its regulators, ie, membrane type-1 of matrix metalloproteinase (MT1-MMP) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and the expression of angiotensin II (Ang II), angiotensin-converting enzyme (ACE), and chymase in young (6.4+/-0.7 years) and old (20.0+/-1.9 years) male monkeys. With advancing age, (1) the intimal thickness increased 3-fold and contained numerous vascular smooth muscle cells and matrix, but no inflammatory cells; (2) the intimal MMP-2 antibody-staining fraction increased by 80% (P<0.01); (3) in situ zymography showed that MMP-2 activity, mainly confined to the intima, increased 3-fold (P<0.01); (4) the MT1-MMP antibody-staining fraction increased by 150% (P<0.001), but the TIMP-2 antibody-staining fraction did not significantly change; (5) steady levels of the mRNA-staining fraction (via in situ hybridization) for MMP-2 increased 7-fold, for MT1-MMP increased 9-fold, and for TIMP-2 increased 2-fold (all P<0.001); and (6) intimal Ang II and ACE immunofluorescence were increased 5-fold and 5.6-fold, respectively, and colocalized with MMP-2. Thus, age-associated arterial remodeling and the development and progression of experimental atherosclerosis in young animals share common mechanisms, ie, MMP-2 activation and increased Ang II signaling. This might explain, in part, the dramatically exaggerated prevalence and severity of vascular diseases with aging.

DOI： 10.1161/01.HYP.0000073843.56046.45

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: To understand further the pathogenesis of familial hypertrophic cardiomyopathy, we determined how the cardiomyopathy induced by an Arg403-->Gln missense mutation in the alpha-myosin heavy chain (403) is affected by chronically enhancing sympathetic drive by mating the mice with those overexpressing G(s)alpha (G(s)alpha x403). METHODS AND RESULTS: Heart rate in 3-month-old conscious mice was elevated similarly (P<0.05) in mice overexpressing G(s)alpha (G(s)alpha mice; 746 +/- 14 bpm) and G(s)alpha x403 mice (718+/- 19 bpm) compared with littermate wild-type mice (WT; 623+/- 18 bpm) and 403 mice (594+/- 16 bpm). Left ventricular ejection fraction (LVEF), as determined by echocardiography, was enhanced in G(s)alpha x403 mice (88+/- 1%, P<0.001) compared with WT (69+/- 1%), 403 (75+/- 1%), and G(s)alpha (69 +/- 2%) mice. Isolated cardiomyocytes from G(s)alpha x403 mice also exhibited higher (P<0.001) baseline percent contraction (11.9+/- 0.5%) than WT (7.0+/- 0.5%), 403 (5.5+/- 0.5%), and G(s)alpha (7.8+/- 0.3%) cardiomyocytes. Relaxation of myocytes was impaired in 403 mice compared with WT but enhanced in G(s)alpha and normalized in G(s)alpha x403 mice. This was also observed in vivo. In vivo isoproterenol (0.1 microgram . kg(-1) . min(-1)) increased LVEF to maximal levels in G(s)alpha x403 and G(s)alpha, whereas in 403, the response was attenuated compared with WT. At 10 months of age, G(s)alpha x403 had significantly depressed LVEF (57 +/- 4%). Histopathological examination demonstrated that myocyte hypertrophy and fibrosis were already present in young G(s)alpha x403 mice and that old animals had severe cardiomyopathy. By 15 months of age, the survival of G(s)alpha x403 was 0% compared with 100% for WT, 71% for G(s)alpha, and 100% for 403 mice (P<0.05). CONCLUSIONS: These results show that the cardiomyopathy developed by G(s)alpha x403 mice is synergistic rather than additive, most likely owing to the elevated baseline function combined with enhanced responsiveness to sympathetic stimulation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1006/jmcc.2001.1413

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.cir.103.19.2382

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/01.atv.20.6.1493

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.res.86.7.802

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.cir.100.20.2113

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Clinical Investigation  

DOI： 10.1172/jci7418

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/s0002-9149(99)00266-0

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Physiological Society  

The goal of this study was to determine the extent to which the effects of milrinone were desensitized in heart failure (HF) and to determine the mechanisms, i.e., whether these effects could be ascribed to changes in cAMP or phosphodiesterase (PDE) activity in HF. Accordingly, we examined the effects of milrinone in seven conscious dogs before and after HF was induced by rapid ventricular pacing at 240 beats/min. The dogs were chronically instrumented for measurements of left ventricular (LV) pressure and first derivative of LV pressure (dP/d t), arterial pressure, LV internal diameter, and wall thickness. Milrinone (10 μg ⋅ kg⁻¹ ⋅ min⁻¹iv) increased LV dP/d t by 1,854 ± 157 from 2,701 ± 105 mmHg/s ( P &lt; 0.05) before HF. After HF the increase in LV dP/d t in response to milrinone was attenuated significantly ( P &lt; 0.05); it increased by 615 ± 67 from 1,550 ± 107 mmHg/s, indicating marked desensitization. In the presence of ganglionic blockade the increases in LV dP/d t (+445 ± 65 mmHg/s) in response to milrinone were markedly less ( P &lt; 0.01), and milrinone increased LV dP/d t even less in HF (+240 ± 65 mmHg/s). cAMP and PDE activity were measured in endocardial and epicardial layers in normal and failing myocardium. cAMP was decreased significantly ( P &lt; 0.05) in LV endocardium (−26%) but not significantly in LV epicardium (−14%). PDE activity was also decreased significantly ( P &lt; 0.05) in LV endocardium (−18%) but not in LV epicardium (−4%). Thus significant desensitization to milrinone was observed in conscious dogs with HF. The major effect was autonomically mediated. The biochemical mechanism appears to be due in part to the modest reductions in PDE activity in failing myocardium, which, in turn, may be a compensatory mechanism to maintain cAMP levels in HF. Reductions in cAMP and PDE levels were restricted to the subendocardium, suggesting that the increased wall stress and reduced coronary reserve play a role in mediating these changes.

DOI： 10.1152/ajpheart.1999.276.5.h1699

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.res.84.6.735

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Clinical Investigation  

DOI： 10.1172/jci4848

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Physiological Society  

The goal of this study was to compare responses to a calcium promoter, BAY y 5959, and dobutamine (Dob) in heart failure (HF). Dogs ( n = 9) were chronically instrumented and studied in the conscious state before and after pacing-induced HF. In the control state, BAY y 5959 (20 μg ⋅ kg⁻¹ ⋅ min⁻¹) increased the first derivative of left ventricular (LV) pressure (dP/d t) by 83 ± 8% and mean arterial pressure (MAP) by 8 ± 2% and decreased heart rate (HR) by 30 ± 3%. With Dob (10 μg ⋅ kg⁻¹ ⋅ min⁻¹) LV dP/d t rose similarly (+80 ± 6%), but HR also rose (+25 ± 4%) ( P &lt; 0.05 vs. BAY y 5959). After HF developed, BAY y 5959 still increased LV dP/d t by 108 ± 8% and MAP by 21 ± 2% and decreased HR by 28 ± 4%, whereas Dob increased LV dP/d t by only 50 ± 7% ( P &lt; 0.05 vs. BAY y 5959) and MAP by 7 ± 3%, and HR did not change (+3 ± 3%) ( P &lt; 0.05 vs. BAY y 5959). In HF, cardiac work increased more ( P &lt; 0.05) with BAY y 5959 (+105 ± 13%) compared with Dob (+47 ± 11%), yet myocardial oxygen consumption increased similarly with the two drugs. Accordingly, mechanical efficiency increased more ( P &lt; 0.05) with BAY y 5959 (+73 ± 14%) than with Dob (+17 ± 12%). These data indicate that 1) increases in contractility mediated directly by Ca²⁺ are relatively resistant to desensitization in HF; and 2) the calcium-channel promoter can produce increases in myocardial contractility and cardiac work similar to those of Dob at a significantly lower oxygen cost, thereby enhancing mechanical efficiency in HF.

DOI： 10.1152/ajpheart.1998.275.6.h2219

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/01.cir.98.13.1342

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）  

DOI： 10.1172/jci1530

CiNii Books

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担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.res.82.4.416

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Physiological Society  

Caveolae, flask-shaped invaginations of cell membranes, are believed to play pivotal roles in transmembrane transportation of molecules and cellular signaling. Caveolin, a structural component of caveolae, interacts directly with G proteins and regulates their function. We investigated the effect of chronic β-adrenergic receptor stimulation on the expression of caveolin subtypes in mouse hearts by immunoblotting and Northern blotting. Caveolin-1 and -3 were abundantly expressed in the heart and skeletal muscles, but not in the brain. Continuous (−)-isoproterenol, but not (+)-isoproterenol, infusion via osmotic minipump (30 μg ⋅ g⁻¹ ⋅ day⁻¹) for 13 days significantly downregulated both caveolin subtypes in the heart. The expression of caveolin-1 was reduced by 48 ± 6.1% and that of caveolin-3 by 28 ± 4.0% ( P &lt; 0.01, n = 8 for each). The subcellular distribution of caveolin subtypes in ventricular myocardium was not altered as determined by sucrose gradient fractionation. In contrast, the expression of both caveolin subtypes in skeletal muscles was not significantly changed. Our data suggest that the expression of caveolin subtypes is regulated by β-adrenergic receptor stimulation in the heart.

DOI： 10.1152/ajpcell.1997.273.6.c1957

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1006/jmcc.1997.0377

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.cir.95.8.2130

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1152/ajpheart.1997.272.2.h753

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Physiological Society  

The goal of this study was to determine whether chronic endogenous sympathetic stimulation resulting from the overexpression of cardiac stimulatory G protein alpha subunit (Gs alpha) in transgenic mice (15.3 +/- 0.1 mo old) resulted in a clinical picture of cardiomyopathy. The left ventricular ejection fraction, measured by echocardiography, was reduced in older mice with Gs alpha overexpression (50.4 +/- 5.4%) compared with age-matched control mice (70.9 +/- 1.6%; P &lt; 0.05). When ejection fractions were compared at similar heart rates, the Gs alpha mice exhibited a greater left ventricular end-diastolic dimension than control mice (4.3 +/- 0.2 vs. 3.7 +/- 0.1 mm; P &lt; 0.05). Baseline heart rates were elevated in conscious Gs alpha mice (722 +/- 27 beats/min; n = 5) compared with control mice (656 +/- 28 beats/min; n = 5). Moreover, electrocardiographic monitoring demonstrated a high incidence of arrhythmias. Increased mortality compared with control mice (31.6 vs. 3.0%; P&lt; 0.01) was also observed. Thus older mice with Gs alpha overexpression exhibit many of the features of dilated cardiomyopathy. This study supports the concept that chronic sympathetic stimulation over an extended period of time, i.e., over the life of an animal, is deleterious and actually may result in cardiomyopathy.

DOI： 10.1152/ajpheart.1997.272.1.h585

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