記述言語：日本語   出版者・発行元：(一社)日本インターベンショナルラジオロジー学会  

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記述言語：日本語   出版者・発行元：(一社)日本インターベンショナルラジオロジー学会  

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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）  

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：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   掲載種別：研究論文（学術雑誌）  

AIMS: Well-controlled mitochondrial homeostasis, including a mitochondria-specific form of autophagy (hereafter referred to as mitophagy), is essential for maintaining cardiac function. The molecular mechanism mediating mitophagy during PO is poorly understood. We have shown previously that mitophagy in the heart is mediated primarily by Atg5/Atg7-independent mechanisms, including Unc-51-like kinase1 (Ulk1)-dependent alternative mitophagy, during myocardial ischemia. Here, we investigated the role of alternative mitophagy in the heart during PO-induced hypertrophy. METHODS AND RESULTS: Mitophagy was observed in the heart in response to transverse aortic constriction (TAC), peaking at 3-5 days. Whereas mitophagy is transiently upregulated by TAC through an Atg7-dependent mechanism in the heart, peaking at 1 day, it is also activated more strongly and with a delayed time course through an Ulk1-dependent mechanism. TAC induced more severe cardiac dysfunction, hypertrophy and fibrosis in ulk1 cardiac specific knock-out (cKO) mice than in wild type mice. Delayed activation of mitophagy was characterized by the co-localization of Rab9 dots and mitochondria and phosphorylation of Rab9 at Ser179, major features of alternative mitophagy. Furthermore, TAC-induced decreases in the mitochondrial aspect ratio were abolished and the irregularity of mitochondrial cristae was exacerbated, suggesting that mitochondrial quality control mechanisms are impaired in ulk1 cKO mice in response to TAC. TAT-Beclin 1 activates mitophagy even in Ulk1-deficient conditions. TAT-Beclin 1 treatment rescued mitochondrial dysfunction and cardiac dysfunction in ulk1 cKO mice during PO. CONCLUSIONS: Ulk1-mediated alternative mitophagy is a major mechanism mediating mitophagy in response to PO and plays an important role in mediating mitochondrial quality control mechanisms and protecting the heart against cardiac dysfunction. TRANSLATIONAL PERSPECTIVE: Heart failure is often accompanied by mitochondrial dysfunction in cardiomyocytes. Elimination of dysfunctional mitochondria by mitochondria-specific forms of autophagy, termed mitophagy, is a crucial mechanism for maintaining mitochondrial function in the stressed heart. We discovered that an unconventional form of mitophagy mediated through an Atg7-independent and Ulk1- and Rab9-dependent mechanism is a predominant form of mitophagy in the heart in response to pressure overload. Interventions to restore mitophagy by stimulating the signaling mechanism of the Ulk1-Rab9-dependent mitophagy should delay the development of heart failure in patients with increased afterload.

DOI： 10.1093/cvr/cvac003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

RATIONALE: Obesity-associated cardiomyopathy characterized by hypertrophy and mitochondrial dysfunction. Mitochondrial quality control mechanisms, including mitophagy, are essential for the maintenance of cardiac function in obesity-associated cardiomyopathy. However, autophagic flux peaks at around 6 weeks of high-fat diet (HFD) consumption and declines thereafter. OBJECTIVE: We investigated whether mitophagy is activated during the chronic phase of cardiomyopathy associated with obesity (obesity cardiomyopathy) after general autophagy is downregulated and, if so, what the underlying mechanism and the functional significance are. METHODS AND RESULTS: Mice were fed either a normal diet or a HFD (60 kcal% fat). Mitophagy, evaluated using Mito-Keima, was increased after 3 weeks of HFD consumption and continued to increase after conventional mechanisms of autophagy were inactivated, at least until 24 weeks. HFD consumption time-dependently upregulated both Ser555-phosphorylated Ulk1 (unc-51 like kinase 1) and Rab9 (Ras-related protein Rab-9) in the mitochondrial fraction. Mitochondria were sequestrated by Rab9-positive ring-like structures in cardiomyocytes isolated from mice after 20 weeks of HFD consumption, consistent with the activation of alternative mitophagy. Increases in mitophagy induced by HFD consumption for 20 weeks were abolished in cardiac-specific ulk1 knockout mouse hearts, in which both diastolic and systolic dysfunction were exacerbated. Rab9 S179A knock-in mice, in which alternative mitophagy is selectively suppressed, exhibited impaired mitophagy and more severe cardiac dysfunction than control mice following HFD consumption for 20 weeks. Overexpression of Rab9 in the heart increased mitophagy and protected against cardiac dysfunction during HFD consumption. HFD-induced activation of Rab9-dependent mitophagy was accompanied by upregulation of TFE3 (transcription factor binding to IGHM enhancer 3), which plays an essential role in transcriptional activation of mitophagy. CONCLUSIONS: Ulk1-Rab9-dependent alternative mitophagy is activated during the chronic phase of HFD consumption and serves as an essential mitochondrial quality control mechanism, thereby protecting the heart against obesity cardiomyopathy.

DOI： 10.1161/CIRCRESAHA.121.319377

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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）  

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）  

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   掲載種別：研究論文（学術雑誌）  

AIMS: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) levels are rarely evaluated simultaneously in the acute phase of acute heart failure (AHF). METHOD AND RESULTS: A total of 1207 AHF patients were enrolled, and 1002 patients were analysed. Blood samples were collected within 15 min of admission. Patients were divided into two groups according to the median value of the NT-proBNP/BNP ratio [low-NT-proBNP/BNP group (Group L) vs. high-NT-proBNP/BNP group (Group H)]. A multivariate logistic regression model showed that the C-reactive protein level (per 1-mg/dL increase), Controlling Nutrition Status score (per 1-point increase), and estimated glomerular filtration rate (eGFR, per 10-mL/min/1.73 m2 increase) were independently associated with Group H [odds ratio (OR) 1.049, 95% confidence interval (CI) 1.009-1.090, OR 1.219, 95% CI 1.140-1.304, and OR 1.543, 95% CI 1.401-1.698, respectively]. A Kaplan-Meier curve analysis showed that the prognosis was significantly poorer in Group H than in Group L, and a multivariate Cox regression model revealed Group H to be an independent predictor of 180-day mortality [hazard ratio (HR) 3.084, 95% CI 1.838-5.175] and HF events (HR 1.963, 95% CI 1.340-2.876). The same trend in the prognostic impact was significantly observed in the low-BNP (<810 pg/mL, n = 501), high-BNP (≥810 pg/mL, n = 501), and low-eGFR (<60 mL/min/1.73 m2, n = 765) cohorts, and tended to be observed in normal-eGFR (≥60 mL/min/1.73 m2, n = 237) cohort. CONCLUSION: A high NT-proBNP/BNP ratio was associated with a non-cardiac condition (e.g. inflammatory reaction, nutritional status, and renal dysfunction) and is independently associated with adverse outcomes in AHF.

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）  

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）  

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）  

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   掲載種別：研究論文（学術雑誌）  

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   掲載種別：研究論文（学術雑誌）  

Lysosomal dysfunction caused by mutations in lysosomal genes results in lysosomal storage disorder (LSD), characterized by accumulation of damaged proteins and organelles in cells and functional abnormalities in major organs, including the heart, skeletal muscle, and liver. In LSD, autophagy is inhibited at the lysosomal degradation step and accumulation of autophagosomes is observed. Enlargement of the left ventricle (LV) and contractile dysfunction were observed in RagA/B cardiac-specific KO (cKO) mice, a mouse model of LSD in which lysosomal acidification is impaired irreversibly. YAP, a downstream effector of the Hippo pathway, was accumulated in RagA/B cKO mouse hearts. Inhibition of YAP ameliorated cardiac hypertrophy and contractile dysfunction and attenuated accumulation of autophagosomes without affecting lysosomal function, suggesting that YAP plays an important role in mediating cardiomyopathy in RagA/B cKO mice. Cardiomyopathy was also alleviated by downregulation of Atg7, an intervention to inhibit autophagy, whereas it was exacerbated by stimulation of autophagy. YAP physically interacted with transcription factor EB (TFEB), a master transcription factor that controls autophagic and lysosomal gene expression, thereby facilitating accumulation of autophagosomes without degradation. These results indicate that accumulation of YAP in the presence of LSD promotes cardiomyopathy by stimulating accumulation of autophagosomes through activation of TFEB.

DOI： 10.1172/JCI143173

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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）  

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   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   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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掲載種別：研究論文（学術雑誌）   出版者・発行元：OAE Publishing Inc.  

DOI： 10.20517/jca.2021.13

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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   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）  

Background: Whether the dose of loop diuretics can be decreased by administration of a sodium-glucose cotransporter 2 (SGLT2) inhibitor in diabetic outpatients with compensated heart failure (HF) is unclear. Methods and Results: This study prospectively enrolled 60 diabetic outpatients with compensated HF. Patients were randomly divided into 2 groups: those administered the SGLT2 inhibitor empagliflozin (n=28) and those not (n=30). Changes in the daily dose of loop diuretics, blood sampling data, and urinary renal tubular biomarkers were evaluated 6 months after the intervention. The median (interquartile range) furosemide dose decreased significantly over the 6-month follow-up period in the empagliflozin group (from 40 [20-40] to 20 [10-20] mg), but not in the non-empagliflozin group (from 23 [20-40] to 40 [20-40] mg). Hemoglobin levels increased significantly in the empagliflozin group (from 13.2 [11.9-14.6] to 14.0 [12.7-15.0] g/dL). In addition, excretion of acetyl-β-D-glucosaminidase decreased significantly over the 6-month follow-up in the empagliflozin group (from 4.8 [2.6-11.7] to 3.3 [2.1-5.4] IU/L), especially in the group in which the dose of loop diuretics decreased (from 4.7 [2.5-14.8] to 3.3 [2.1-4.5] IU/L). Conclusions: Empagliflozin administration decreased the dose of loop diuretics and increased the production of erythropoietin, which may help prevent renal tubular injury in diabetic outpatients with HF.

DOI： 10.1253/circrep.CR-20-0041

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The impact of elevated total bilirubin (Tbil) levels on adverse clinical outcomes in patients with acute heart failure (HF) has not been fully established, although liver damage is common among these patients. We therefore examined the associations between Tbil levels at admission and systolic blood pressure (SBP) in patients with acute HF in an emergency setting and to evaluate clinical outcomes related to elevated Tbil, particularly in patients with SBP < 100 mmHg. Clinical data and outcomes in acute HF patients (n = 877) were compared according to Tbil quartiles. SBP values < 100 mmHg were more prevalent among patients in the highest quartile (Tbil ≥ 1.0 mg/dL) vs. others (15.4% vs. 3.1%, p < 0.001). Tbil levels were inversely and significantly correlated with SBP at admission (Spearman's ρ, - 0.243; p < 0.001). Kaplan-Meier estimate survival curves showed that event-free survival was worse among patients in the highest Tbil quartile vs. others (78.5% vs. 90.4%, p < 0.001). When comparing survival rates among patients in SBP < 100 mmHg (n = 50), the difference of survival rate became larger for the patients in the highest quartile (n = 29) vs. others (n = 21) (41.4% vs. 77.7%, p < 0.001). Multivariate Cox proportional hazard analysis showed that Tbil ≥ 1.3 mg/dL, not SBP or B-type natriuretic peptide, independently and significantly predicted cardiac death within 180 days in acute HF patients with SBP < 100 mmHg (hazard ratio 3.74; 95% confidence interval 1.39-10.05; p < 0.001). In conclusion, Tbil levels were inversely correlated with SBP at admission in patients with acute HF. Tbil levels independently predicted the risk of 180-day cardiac mortality, especially in acute HF patients with SBP < 100 mmHg.

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: The factors associated with a low plasma xanthine oxidoreductase (XOR) activity were not elucidated in patients with acute heart failure (AHF). METHODS: Two-hundred and twenty-nine AHF patients who visited the emergency department were prospectively analyzed. AHF patients were divided into 3 groups according to the plasma XOR quartiles (Q1 = low-XOR group [n = 57], Q2/Q3 = middle-XOR group [n = 115], and Q4 = high-XOR group [n = 57]). The prognostic nutritional index (PNI) and the controlling nutritional status (CONUT) score were evaluated. RESULTS: The multivariate logistic regression model showed that the nutritional status (PNI: OR 1.044, 95% CI 1.000-1.088; CONUT: OR 3.805, 95% CI 1.158-12.498), age, and serum creatinine level were independently associated with a low plasma XOR activity. The Kaplan-Meier curve showed a significantly lower incidence of heart failure events in the low-XOR group than in the middle + high-XOR group (hazard ratio, HR 1.648, 95% CI 1.061-2.559). In particular, a low XOR activity with an increased serum creatinine level (>1.21 mg/dL) was independently associated with heart failure events (HR 1.937, 95% CI 1.199-3.130). CONCLUSION: A low plasma XOR activity was associated with malnutrition, renal dysfunction, and aging in AHF. A low XOR activity complicated with renal dysfunction leads to adverse long-term outcomes.

DOI： 10.1159/000508037

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hyperuricemia is known to be associated with adverse outcomes in cardiovascular intensive care patients, but its mechanisms are unknown. A total of 569 emergency department patients were prospectively analyzed and assigned to intensive care (ICU group, n = 431) or other departments (n = 138). Uric acid (UA) levels were significantly higher in the intensive care patients (6.3 [5.1-7.6] mg/dl vs. 5.8 [4.6-6.8] mg/dL). The plasma xanthine oxidoreductase (XOR) activity in the ICU group (68.3 [21.2-359.5] pmol/h/mL) was also significantly higher than that in other departments (37.2 [15.1-93.6] pmol/h/mL). Intensive care patients were divided into three groups according to plasma XOR quartiles (Q1, low-XOR, Q2/Q3, normal-XOR, and Q4, high-XOR group). A multivariate logistic regression model showed that lactate (per 1.0 mmol/L increase, OR 1.326; 95%, CI 1.166-1.508, p < 0.001) and the Acute Physiology and Chronic Health Evaluation II score (per 1.0 point increase, OR 1.095, 95% CI 1.034-1.160, p = 0.002) were independently associated with the high-XOR group. In-hospital mortality was significantly higher in the high-XOR group (n = 28, 26.2%) than in the normal- (n = 11, 5.1%) and low- (n = 9, 8.3%) XOR groups. The high-XOR group (vs. normal-XOR group) was independently associated with the in-hospital mortality (OR 2.934; 95% CI 1.170-7.358; p = 0.022). Serum UA levels and plasma XOR activity were high in patients admitted to intensive care. The enhanced XOR activity may be one of the mechanisms under which hyperuricemia was associated with adverse outcomes in patients requiring cardiovascular intensive care.

DOI： 10.1007/s00380-020-01608-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mechanisms of urgently presenting acute heart failure (AHF) are not clear. We evaluated the serum catecholamine values of AHF patients immediately after admission. A total of 1,475 AHF patients were screened, and 484 who were admitted from their homes and in whom serum catecholamine could be evaluated immediately after admission were analyzed. The patients were divided into three groups according to the time interval from the onset of symptoms to admission (OA): < 3 hours (early-OA group; n = 283), 3-24 hours (middle-OA group; n = 142), and ≥24 hours (late-OA group; n = 59). In the early-OA group, the systolic blood pressure (SBP) was significantly higher, orthopnea was more frequent, the pH value was significantly decreased, and the use of noninvasive positive-pressure ventilation was required significantly more often than in the other groups. The serum noradrenaline level was significantly increased in the early-OA group (1.96 [1.02-3.60] ng/mL) than in the middle-OA (1.49 [0.73-3.41] ng/mL) and late-OA (1.40 [0.91-2.42] ng/mL) groups, and the adrenaline level was significantly increased in the early-OA group (0.36 [0.13-1.17] ng/mL) than in the late-OA (0.22 [0.09-0.52] ng/mL) group. A multivariate logistic regression model indicated the early-OA group was independently associated with the SBP > 140 mmHg (odds ratio [OR]: 2.219, 95% CI: 1.375-3.581), midnight/early morning admission (OR: 3.158, 95% CI: 2.048-4.868), and high serum catecholamine value (adrenaline > 0.96 ng/mL, noradrenaline > 3.39 ng/mL, and dopamine > 0.21 ng/mL) (OR 2.091, 95% CI: 1.161-3.767). In conclusion, urgently presented AHF might be induced by an endogenous catecholamine surge, which causes an excessive rise in blood pressure leading to increased after-overload and volume-shift lung congestion.

DOI： 10.1536/ihj.19-523

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUNDS: The prevalence of atrial fibrillation (AF) has been increasing in aging societies. The prognostic impact of AF associated with worsening heart failure (HF) remains obscure. METHODS AND RESULTS: We analyzed 1170 acute heart failure (AHF) patients who required intensive care. Patients were assigned to two groups according to the prevalence of AF: no episode of AF (n = 940) and pre-existing AF (Group-1, n = 230). Patients with no episode of AF (n = 940) were further divided into two groups according to presence of new-onset of AF after admission (Group-2a, n = 258) or not (Group-2b, n = 682). Kaplan-Meier curve analysis showed that prognosis, including all-cause mortality and HF-events within 1000 days, was significantly poorer in the Group-1 compared to the Group-2b. However, a multivariate Cox regression model showed that the Group-1 was not an independent predictor of 1000-day mortality and HF-events. Furthermore, Kaplan-Meier curve analysis showed that prognosis, including all-cause mortality and HF-events within 1000 days, was significantly poorer in the Group-2a than in the Group-2b. A multivariate Cox regression model revealed that the Group-2a was an independent predictor of 1000-day mortality (HR: 1.403, 95% CI: 1.018-1.934) and HF-events (HR: 1.352, 95% CI: 1.071-1.708). A multivariate logistic regression model showed that only age (≥75 years old) was independently associated with new-onset of AF after admission (odds ratio: 1.556, 95% CI: 1.130-2.143). CONCLUSIONS: New-onset AF associated with worsening HF increases with age and is independently-associated with adverse outcome in patients with AHF.

DOI： 10.1016/j.ijcard.2019.09.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Low triiodothyronine (T3) syndrome has recently been evaluated as a prognostic marker of acute heart failure (AHF). However, in which cases low T3 syndrome typically leads to adverse outcomes remain unclear. Of 1,432 AHF patients screened, 1,190 were enrolled. Euthyroidism was present in 956 patients (80.3%), who were divided into 2 groups: the normal group (n = 445, FT3 ≥1.88 µIU/L) and low-FT3 group (n = 511, FT3 <1.88 µIU/L). The survival rates and event-free rates within 365 days were significantly lower in the low-FT3 group than in the normal group. A multivariate Cox regression model showed that the low-FT3 group was an independent predictor of 365-day mortality (hazard ratio [HR] 1.429, 95% confidence interval [CI] 1.013 to 2.015) and HF events (HR 1.349, 95% CI 1.047 to 1.739). The multivariate logistic regression analysis revealed that age (per 10-year old increase, odds ratio [OR]: 1.186, 95% CI: 1.046 to 1.345) and prognostic nutritional index (PNI; per 1-point increase, OR: 1.067, 95% CI: 1.046 to 1.089) were independently associated with the low-FT3 group. The prognosis in patients with a low PNI and over 75 years old, including all-cause death within 365 days, was significantly poorer in the low-FT3 group than in the normal group. In conclusion, adverse outcomes were predicted by the presence of low T3. AHF patients with low T3 syndrome are strongly associated with aging and malnutrition. Low T3 syndrome complicated with older age and malnutrition is likely to lead to adverse outcomes in patients with AHF.

DOI： 10.1016/j.amjcard.2019.10.051

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The length of hospital stay (LOHS) after acute heart failure (AHF) is too long in Japan. The clinical approach to shortening LOHS is an urgent issue in the aging Japanese society. Methods and Results: Of 1,473 AHF patients screened, 596 patients >75 years old were enrolled. They were divided by LOHS: <28 days (<28-day group, n=316) and ≥28 days (≥28-day group, n=280). Systolic blood pressure and serum hemoglobin were significantly higher and serum blood urea nitrogen and creatinine significantly lower in the <28-day group than in the ≥28-day group. Non-invasive positive pressure ventilation (NPPV) use was significantly more frequent in the <28-day group than in the ≥28-day group. Furthermore, newly initiated tolvaptan in <12 h was significantly more frequent in the <28-day group than in the ≥28-day group (P=0.004). On multivariate logistic regression analysis, newly initiated tolvaptan in <12 h (OR, 2.574; 95% CI: 1.146-5.780, P=0.022) and NPPV use (OR, 1.817; 95% CI: 1.254-2.634, P=0.002) were independently associated with the <28-day group. The same result was found after propensity score matching for LOHS. Conclusions: LOHS was prolonged in patients with severe HF but could be shortened by early tolvaptan treatment.

DOI： 10.1253/circrep.CR-19-0132

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The mechanisms of the increased plasma xanthine oxidoreductase (XOR) activity in outpatients with cardiovascular disease were unclear. Methods and Results: A total of 372 outpatients were screened, and 301 outpatients with cardiovascular disease were prospectively analyzed. Blood samples were collected from patients who visited a daily cardiovascular outpatient clinic. Patients with diabetes mellitus (DM) were significantly more likely to be classified into the high-XOR group (≥100 pg/h/mL; 50%) than the low-XOR group (<100 pmol/h/mL; 28.7%). On multivariate logistic regression analysis, DM (OR, 2.683; 95% CI: 1.441-4.996) was independently associated with high plasma XOR activity in all cohorts. In the diabetic cardiovascular disease patients (n=100), median body mass index (BMI) in the high-XOR group (28.0 kg/m2; IQR, 25.2-29.4 kg/m2, n=32) was significantly higher than in the low-XOR group (23.6 kg/m2; IQR, 21.2-25.7 kg/m2, n=68), and BMI was independently associated with high plasma XOR activity (OR, 1.340; 95% CI: 1.149-1.540). Plasma hydrogen peroxide was significantly higher in DM patients with high plasma XOR activity and obesity (>22 kg/m2) than in other patients. Conclusions: DM with obesity is one of the mechanisms of XOR enhancement in cardiovascular disease. The increase of XOR is a possible pathway for the production of reactive oxygen species in obese cardiovascular disease patients with DM.

DOI： 10.1253/circrep.CR-19-0116

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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）  

DOI： 10.1016/j.amjcard.2019.06.025

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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.amjcard.2019.03.045

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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.ijcha.2019.03.005

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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.2757-19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

RATIONALE: Diabetic patients develop cardiomyopathy characterized by hypertrophy, diastolic dysfunction, and intracellular lipid accumulation, termed lipotoxicity. Diabetic hearts utilize fatty acids as a major energy source, which produces high levels of oxidative stress, thereby inducing mitochondrial dysfunction. OBJECTIVE: To elucidate how mitochondrial function is regulated in diabetic cardiomyopathy. METHODS AND RESULTS: Mice were fed either a normal diet or high-fat diet (HFD, 60 kcal % fat). Although autophagic flux was activated by HFD consumption, peaking at 6 weeks ( P<0.05), it was attenuated thereafter. Mitophagy, evaluated with Mito-Keima, was increased after 3 weeks of HFD feeding (mitophagy area: 8.3% per cell with normal diet and 12.4% with HFD) and continued to increase even after 2 months ( P<0.05). By isolating adult cardiomyocytes from GFP-LC3 mice fed HFD, we confirmed that mitochondria were sequestrated by LC3-positive autophagosomes during mitophagy. In wild-type mice, cardiac hypertrophy, diastolic dysfunction (end diastolic pressure-volume relationship =0.051±0.009 in normal diet and 0.11±0.004 in HFD) and lipid accumulation occurred within 2 months of HFD feeding ( P<0.05). Deletion of atg7 impaired mitophagy, increased lipid accumulation, exacerbated diastolic dysfunction (end diastolic pressure-volume relationship =0.11±0.004 in wild type and 0.152±0.019 in atg7 cKO; P<0.05) and induced systolic dysfunction (end systolic pressure-volume relationship =24.86±2.46 in wild type and 15.93±1.76 in atg7 cKO; P<0.05) during HFD feeding. Deletion of Parkin partially inhibited mitophagy, increased lipid accumulation and exacerbated diastolic dysfunction (end diastolic pressure-volume relationship =0.124±0.005 in wild type and 0.176±0.018 in Parkin KO, P<0.05) in response to HFD feeding. Injection of TB1 (Tat-Beclin1) activated mitophagy, attenuated mitochondrial dysfunction, decreased lipid accumulation, and protected against cardiac diastolic dysfunction (end diastolic pressure-volume relationship =0.110±0.009 in Control peptide and 0.078±0.015 in TB1, P<0.05) during HFD feeding. CONCLUSIONS: Mitophagy serves as an essential quality control mechanism for mitochondria in the heart during HFD consumption. Impairment of mitophagy induces mitochondrial dysfunction and lipid accumulation, thereby exacerbating diabetic cardiomyopathy. Conversely, activation of mitophagy protects against HFD-induced diabetic cardiomyopathy.

DOI： 10.1161/CIRCRESAHA.118.314607

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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/ehf2.12390

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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/ehf2.12414

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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/CIRCHEARTFAILURE.118.005529

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1074/jbc.RA118.006123

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background:
The features of sleep-associated acute heart failure (AHF) patients admitted at midnight or early morning (M/E) are unclear.
Methods and Results:
Of 1,268 AHF patients screened, 932 were analyzed, and divided into 2 groups by admission time (M/E group, 23:00-06:59, n=399; daytime group, 07:00-22:59, n=533). Those in the M/E group were further divided by the presence of a prodrome: with (n=176; prodrome group) or without (n=223; sudden onset group). The median time from symptom onset to hospitalization was significantly shorter in the M/E group (98 min; range, 65-170 min) than in the daytime group (123 min; range, 68-246 min). The 365-day HF event rate in the M/E group was significantly lower than that of the daytime group. On multivariate logistic regression modeling the M/E group was independently associated with a better outcome than the daytime group (OR, 0.673; 95% CI: 0.500-0.905). In the M/E group, the 365-day HF event rate was significantly lower in the prodrome group than in the sudden onset group. On multivariate logistic regression modeling, inclusion in the prodrome group was independently associated with a better outcome (OR, 0.544; 95% CI: 0.338-0.877).
Conclusions:
AHF patients admitted during sleeping hours were not sicker than those admitted during the daytime. The absence of a prodrome, however, might be associated with future repeated HF events.

DOI： 10.1253/circrep.CJ-18-0014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/2048872618822473

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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.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）  

AIMS: Coronary angioscopy (CAS) is a robust imaging methodology for evaluation of vascular healing response after stenting. However, the procedure requires a guiding catheter with a diameter of more than 6 Fr, which is rather invasive at follow-up angiography. Recently, coronary angioscopes of a smaller diameter have been able to pass through a 4 Fr guiding catheter. This study aimed to investigate the feasibility and safety of slender CAS observation using a 4 Fr guiding catheter. METHODS AND RESULTS: Thirty-three consecutive patients who underwent follow-up angiography were evaluated. Following usual angiography via the radial artery, the stent segment was observed by non-occlusive CAS through a 4 Fr guiding catheter. Low molecular weight dextran-L (4 mL/sec) was flushed from a guiding catheter to replace coronary blood. The success rate, anatomical or procedural factors related to the success, and incidence of adverse events were examined. The success rate was 84.8% (n=28/33). The luminal diameter at the orifice of the target vessel was larger in the successful than in the failed group (4.03±0.61 mm vs. 3.39±0.61 mm, respectively; p=0.009). The presence of deep engagement of the guiding catheter into the target vessel was a key factor for sufficient observation (100% in the successful group vs. 0% in the failed group; p<0.0001). No adverse events, such as dissection or acute coronary syndrome, were reported. CONCLUSIONS: The new method of CAS through a 4 Fr guiding catheter demonstrated high feasibility and safety. This less invasive observation via CAS may be useful for stent follow-up.

DOI： 10.4244/AIJ-D-18-00003

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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 College of Cardiology (Nippon-Sinzobyo-Gakkai)  

Background: The association between social factors and the long-term prognosis of acute heart failure (AHF) remains unclear. Methods and results: One thousand fifty-one AHF patients were screened, and 915 were enrolled. Four hundred forty-two AHF patients ≥75 years of age (the elderly cohort) were also included in a sub-analysis. Participants who fulfilled one of the three marital status-, offspring-, and living status-related criteria were considered socially vulnerable. On this basis they were classified into the socially vulnerable (n = 396) and non-socially vulnerable (n = 519) groups in the overall cohort, and the socially vulnerable (n = 219) and non-socially vulnerable (n = 223) groups in the elderly cohort. 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 overall (p = 0.049) and elderly (p = 0.004) cohorts. A multivariate Cox regression model revealed that social vulnerability was an independent predictor of 1000-day mortality in the overall [hazard ratio (HR): 1.340, 95% confidence interval (CI): 1.003–1.043, p = 0.048] and elderly cohort (HR: 1.531, 95% CI: 1.027–2.280, p = 0.036). Regarding the components of social vulnerability, the marital status was an independent factor in the elderly cohort (HR: 1.500, 95% CI 1.043–2.157, p = 0.029). Conclusion: Social vulnerability was independently associated with long-term outcomes in AHF patients, especially in the elderly cohort. Organization of the social structure of AHF patients might be able to improve their prognosis.

DOI： 10.1016/j.jjcc.2018.01.014

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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 Inc.  

The aims of the present study were to elucidate features of culprit lesion plaque morphology using optical coherence tomography (OCT) in relation to elevated serum uric acid (sUA) levels and to clarify the impact of sUA levels on adverse clinical outcomes in patients with acute coronary syndrome (ACS). Clinical data and outcomes were compared between ACS patients with sUA ≥6 mg/dl (high-sUA
n = 506) and sUA &lt
6.0 mg/dl (low-sUA
n = 608). Angiography and OCT findings were analyzed in patients with preintervention OCT and compared between groups of high-sUA (n = 206) and low-sUA (n = 273). Patients with high-sUA were more frequently male (88% vs 74%, p &lt
0.001), younger (median 65 years vs 67 years, p = 0.017), more obese (median body mass index
24.3 kg/m2 vs 23.2 kg/m2, p &lt
0.001), and had a more frequent history of hypertension (72% vs 62%, p &lt
0.001). ACS with lung congestion or cardiogenic shock was more prevalent in patients with high-sUA (30% vs 13%, p &lt
0.001). Plaque rupture (54% vs 42%, p = 0.021) and red thrombi (55% vs 41%, p = 0.010) were more prevalently observed by OCT in patients with high-sUA. Kaplan–Meier estimate survival curves showed that the 2-year cardiac mortality was higher in patients with high-sUA (12.1% vs 4.2%, p &lt
0.001). The multivariate Cox proportional hazard analysis showed that sUA values independently and significantly predicted cardiac death within 2 years (hazard ratio 1.41 [95% confidence interval 1.26 to 1.57], p &lt
0.001). In conclusion, sUA levels are associated with culprit lesion coronary plaque morphology and raised sUA levels affect cardiovascular mortality after adjusting for several cardiovascular risk factors.

DOI： 10.1016/j.amjcard.2018.03.022

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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：Springer Tokyo  

Atherosclerotic diseases sometimes contribute to acute heart failure (AHF). The aim of the present study is to elucidate the prognostic impact of AHF with atherosclerosis. A total of 1226 AHF patients admitted to the intensive care unit were analyzed. AHF associated with atherosclerosis was defined by the etiology: atherosclerosis-AHF group (n = 708) (patients whose etiologies were ischemic heart disease or hypertensive heart disease) or AHF not associated with atherosclerosis (non-atherosclerosis-AHF) group (n = 518). Kaplan–Meier curves showed that the survival rate of the atherosclerosis-AHF group was significantly better than that of the non-atherosclerosis-AHF group within 730 days of follow-up. Regarding pre-hospital medications, atherosclerosis-AHF patients were more likely to be administered nitroglycerin (20.3 vs. 13.7%, p = 0.003), nicorandil (18.8 vs. 7.5%, p &lt
0.001), angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) (46.5 vs. 38.6%, p = 0.006), β-blocker (33.2 vs. 26.6%, p = 0.014) and statin (30.1 vs. 22.4%, p = 0.003) because of a previous coronary event or atherosclerotic diseases. In sub-group analysis of medication including administered ≥ 3 drugs within 5 medications and ACE-I/ARB, atherosclerosis-AHF significantly decreased the rate of all-cause death within 180 days (hazard ratio (HR) 0.215, 95% CI 0.078–0.593 and HR 0.395, 95% CI 0.244–0.641, respectively) with a significant interaction (p value for interaction 0.022 and 0.005, respectively). Kaplan–Meier curves showed that the 180-days survival rate of the atherosclerosis-AHF group with ACE-I/ARB and ≥ 3 drugs were significantly better than other groups. The AHF patients associated with atherosclerosis lead to be a good long-term outcome. A relationship may exist between efficient treatment including ACE-Is before admission and a good outcome in mid-term.

DOI： 10.1007/s00380-018-1204-7

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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/ehf2.12264

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DOI： 10.1016/j.jacc.2018.02.066

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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：Springer Tokyo  

The prognostic impact of a decreased blood glucose level in acute heart failure (AHF) has not been sufficiently clarified. The data from 1234 AHF patients were examined in the present study. The blood glucose (BG) levels were evaluated at admission. The patients were divided into groups based on the following: with or without diabetes mellitus (DM), and BG level ≥ 200 mg/dl (elevated BG) or &lt
200 mg/dl (decreased BG). The elevated and decreased BG patients were further divided into another three groups: 200 mg/ml ≤ BG &lt
300 mg/dl (mild-elevated), 300 mg/ml ≤ BG &lt
400 mg/dl (moderate-elevated) and BG ≥ 400 mg/ml (severe-elevated)
and 150 mg/ml ≤ BG &lt
200 mg/dl (mild-decreased), 100 mg/ml ≤ BG &lt
150 mg/dl (moderate-decreased) and BG &lt
100 mg/ml (severe-decreased), respectively. The DM patients had a significantly poorer mortality than the non-DM patients. The prognosis was different between patients with elevated or decreased BG. In DM patients with elevated BG, the severe-elevated patients had a significantly poorer prognosis than moderate- and mild-elevated patients. In the DM patients with decreased BG, the severe-decreased patients had a significantly poorer prognosis than those moderate- and mild-decreased patients. The multivariate Cox regression model showed that a severe-decreased [hazard ratio (HR) 3.245, 95% confidence interval (CI) 1.271–8.282] and severe-elevated (HR 2.300, 95% CI 1.143–4.628) status were independent predictors of 365-day mortality in AHF patients with DM. The mortality was high among AHF patients with DM. Furthermore, both severe hyperglycemia and hypoglycemia were independent predictors of the mortality in patients with AHF complicated with DM.

DOI： 10.1007/s00380-018-1151-3

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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：Springer Tokyo  

The optimum method of managing anemia during the acute phase of acute heart failure (AHF) remains to be elucidated. The data from 1109 AHF patients were enrolled in present study. The hemoglobin (Hb) levels were evaluated in all patients at admission (day 1) and 3 days after admission (day 3), and in survival discharge patients (n = 998) before discharge (pre-discharge). The serum hemoglobin levels were significantly lower on day 3 (11.2 (9.6–12.9) g/dl) than on day 1 (12.4 (10.4–14.2) g/dl) and at pre-discharge (11.6 (10.1–13.2) g/dl). A multivariate Cox regression model showed that mild anemia (11.0 ≤ Hb ≤ 12.9 g/dl, n = 316) and severe anemia (Hb ≤ 10.9 g/dl, n = 517) on day 3 were independent predictors of HF event (hazard ratio (HR) 1.542, 95% confidence interval (CI)1.070–2.221, HR 2.026, 95% CI 1.439–2.853), and severe anemia on day 3 were independent predictors of 365-day mortality (HR 2.247, 95% CI 1.376–3.670). The prognosis, including all-cause death and HF events, in patients with non-anemia on day 1 was significantly poorer in severe new-anemia patients on day 3 (n = 44) than in mild new-anemia patients on day 3 (n = 153) and non-anemia patients on day 3 (n = 252). In patients with anemia on day 1, the prognosis was significantly poorer in patients with severe anemia on day 3 (n = 190) than in those with non-anemia or mild anemia on day 3 (n = 482). The hemoglobin level after the initial treatment might be easily influenced by clinical decongestion. Successfully treated decongestion can help maintain the hemoglobin levels. It, therefore, leads to a prognostic benefit in patients with AHF. These findings might underscore the importance of hemoglobin management of the acute phase of AHF.

DOI： 10.1007/s00380-017-1057-5

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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  

Objectives: We sought to clarify clinical features and outcomes related to calcified nodules (CN) compared with plaque rupture (PR) and plaque erosion (PE) detected by optical coherence tomography (OCT) at the culprit lesions in patients with acute coronary syndrome (ACS). Methods: Based on OCT findings for culprit lesion plaque morphologies, ACS patients with analyzable OCT images (n = 362) were classified as CN, PR, PE, and other. Results: The prevalence of CN, PR, and PE was 6% (n = 21), 45% (n = 163), and 41% (n = 149), respectively. Patients with CN were older (median 71 vs. 65 years, p = 0.03) and more diabetic (71 vs. 35%, p = 0.002) than those without CN. In OCT findings, the distal reference lumen cross-sectional area (median 4.2 vs. 5.2 mm2, p = 0.048) and the postintervention minimum lumen cross-sectional area (median 4.5 vs. 5.3 mm2, p = 0.04) were smaller in lesions with CN than in those without. Kaplan-Meier estimate survival curves showed that the 500-day survival without target lesion revascularization (TLR) was lower (p = 0.011) for patients with CN (72.9%) than for those with PR (89.3%) or PE (94.8%). Conclusions: ACS patients with CN at the culprit lesion had more TLR compared to those with PR or PE.

DOI： 10.1159/000481931

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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：Springer Tokyo  

Patients with heart failure (HF) are sometimes classified as malnourished, but the prognostic value of nutritional status in acute HF (AHF) remains largely unstudied. 1214 patients who were admitted to the intensive care unit between January 2000 and June 2016 were screened based on their serum albumin, lymphocyte count, and total cholesterol measures. A total of 458 HF patients were enrolled in this study. The Prognostic Nutritional Index (PNI) is calculated as 10 × serum albumin (g/dL) + 0.005 × lymphocyte count (per mm3) (lower = worse). The Controlling Nutritional Status (CONUT) score is points based, and is calculated using serum albumin, total cholesterol, and lymphocyte count (range 0–12, higher = worse). Patients were divided into three groups according to PNI: high-PNI (PNI &lt
 35, n = 331), middle-PNI (35 ≤ PNI &lt
 38, n = 50), and low-PNI (PNI ≥ 38, n = 77). They were also divided into four groups according to CONUT score: normal-CONUT (0–1, n = 128), mild-CONUT (2–4, n = 179), moderate-CONUT (5–8, n = 127), and severe-CONUT (≥9, n = 24). The PNI, which exhibited a good balance between sensitivity and specificity for predicting in-hospital mortality [66.1 and 68.4%, respectively
area under the curve (AUC) 0.716
95% confidence interval (CI) 0.638–0.793), was 39.7 overall, while the CONUT score was 5 overall (61.4 and 68.4%, respectively
AUC 0.697
95% CI 0.618–0.775). A Kaplan–Meier curve indicated that the prognosis, including all-cause death, was significantly (p &lt
 0.001) poorer in low-PNI patients than in high-PNI groups and was also significantly poorer in severe-CONUT patients than in normal-CONUT and mild-CONUT groups. A multivariate Cox regression model showed that the low-PNI and severe-CONUT categories were independent predictors of 365-day mortality [hazard ratio (HR) 2.060, 95% CI 1.302–3.259 and HR 2.238, 95% CI 1.050–4.772, respectively). Malnutrition, as assessed using both the PNI and the CONUT score, has a prognostic impact in patients with severely decompensated AHF.

DOI： 10.1007/s00380-017-1034-z

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記述言語：日本語   出版者・発行元：(一社)日本集中治療医学会  

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DOI： 10.1159/000496053

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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 SCIENCE BV  

Background: The gender differences in the prognosis of Asian patients with acute heart failure (AHF) remain to be elucidated.
Methods and results: One thousand fifty AHF patients were enrolled. The patients were assigned to a female group (n = 354) and a male group (n = 696). A Kaplan-Meier curve showed that the cardiovascular survival rate of the female group was significantly lower than that of the male group (p = 0.005). A multivariate Cox regression model identified female gender [hazard ratio (HR): 1.381, 95% CI: 1.018-1.872] as an independent predictor of 730-day cardiovascular death. In subgroup analysis by age, in patients over 79 years, female gender significantly increased the cardiovascular death (HR: 1.715, 95% CI: 1.088-2.074, p &lt; 0.001) with a significant interaction (p-value for interaction &lt; 0.001). The prognosis, including cardiovascular death, was significantly poorer among elderly female patients (&gt;= 79 years) than among elderly male patients (p = 0.019). The multivariate Cox regression model identified female gender as an independent predictor of 730-day cardiovascular death in patients who were older than 79 years of age (HR, 1.943; 95% CI, 1.192-3.167).
Conclusions: Female gender was associated with poor prognosis in AHF patients. In particular, old age (&gt;= 79 years) was associated with adverse outcomes in female patients with AHF. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2016.11.015

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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：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）   出版者・発行元：SPRINGER  

Obesity is known to be associated with the development of heart failure (HF). However, the relationship between the body mass index (BMI) and acute HF (AHF) remains to be elucidated. Eight hundred and eight AIIF patients were enrolled in this study. The patients were assigned to four groups according to their BMI values: severely thin (n = 11, BMI &lt;16), normal/underweight (n = 579, 16 = BMI &lt;25), overweight (n = 178, 25 = BMI &lt;30) and obese (n = 40, BMI = 30). The patients in the severely thin group were more likely to be female, have systolic blood pressure (SBP) &lt;100 mmHg and have valvular disease than normal/underweight patients. The patients in the overweight group were significantly younger than those in the normal/underweight, and those in the overweight group were more likely to have SBP = 140 mmHg and hypertensive heart disease and less likely to have valvular disease than the patients in the normal/underweight group. The prognosis, including all-cause death, was significantly poorer among patients who were severely thin than those who were normal/underweight, overweight and significantly better among those who were overweight than those who were normal/underweight, severely thin and obese patients. A multivariate Cox regression model identified that severely thin [HR: 3.372, 95% confidence interval (CI) 1.362-8.351] and overweight ( HR: 0.615, 95% CI 0.391-0.966) were independent predictors of 910-day mortality as the reference of normal/underweight. Overweight patients tended to have SBP &gt;= 140 mmHg and be relatively young, while severely thin patients tended to have SBP &lt;100 mmHg and be female. These factors were associated with a better prognosis of overweight patients and adverse outcomes in severely thin patients. These factors may contribute to the "obesity paradox" in severely decompensated AHF patients.

DOI： 10.1007/s00380-016-0908-9

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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：SPRINGER  

Atherosclerosis induces the elevation of uric acid (UA), and an elevated UA level is well known to lead to a poor prognosis in patients with acute heart failure (AHF). However, the prognostic value of atherosclerotic risk factors in hyperuricemic AHF patients remains to be elucidated. The data from 928 patients who were admitted to the intensive care unit (ICU) at Nippon Medical School Chiba Hokusoh Hospital between January 2001 and December 2014, and whose serum UA levels were measured were screened. A total of 394 AHF patients with hyperuricemia were enrolled in this study. The patients were assigned to a low-risk group (&lt;= 1 atherosclerosis risk factor) and a high-risk group (&gt;= 2 atherosclerosis risk factors) according to their number of risk factors. The patients in the low-risk group were more likely to have dilated cardiomyopathy, clinical scenario 3 than those in the high-risk group. The serum total bilirubin, blood urea nitrogen, C-reactive protein, and brain-type natriuretic peptide levels were significantly higher in the low-risk group than the high-risk group (p &lt; 0.001, p = 0.005, p = 0.003, and p = 0.008, respectively). A multivariate Cox regression model revealed that the number of risk factors (number = 1, HR (hazard ratio) 0.243, 95 % CI 0.096-0.618, p = 0.003; number = 2, HR 0.253, 95 % CI 0.108-0.593, p = 0.002; number &gt;= 3, HR 0.209, 95 % CI 0.093-0.472, p &lt; 0.001), eGFR (per 1.0 mmol/l increase) (HR 0.977, 95 % CI 0.961-0.994, p = 0.007), and serum UA level (per 1 mg/dl increase) (HR 1.270, 95 % CI 1.123-1.435, p &lt; 0.001) was an independent predictor of 1-year mortality. The prognosis, including all-cause death and HF events, was significantly poorer among the low-risk patients than among the high-risk patients. Atherosclerotic risk factors were not associated with a poor prognosis in patients with hyperuricemic AHF.

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：KARGER  

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 x 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. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000477825

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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 SCIENCE BV  

Background: The serum level of uric acid (UA) is a well-known prognostic factor for heart failure (HF) patients. However, the prognostic impact of hyperuricemia and the factors that induce hyperuricemia in acute I-IF (AHF) patients are not well understood.
Methods and results: Eight hundred eighty-nine AHF patients were enrolled in this study. The patients were assigned into a low UA group (UA &lt;= 7.0 mg/dl, n = 495) or a high UA group (UA &gt; 7.0 mg/dl, n = 394) according to their UA level on admission. A Kaplan-Meier curve showed that the survival rate of the low UA group was significantly higher than that of the high UA group. A multivariate Cox regression model identified that a high UA level (HR: 1.192, 95%CI 1.112-1.277) was an independent predictor of 180-day mortality. A multivariate logistic regression model for a high serum UA level on admission indicated that chronic kidney disease (CKD) (OR: 2.030, 95%CI: 1.298-3.176, p = 0.002) and the administration of loop diuretics before admission (OR: 1.556, 95%Cl: 1.010-2.397, p = 0.045) were independent factors. The prognosis, including all-cause death and HF events, was significantly poorer among patients who had a high UA level who had previously used loop diuretics and among CKD patients with a high UA level than among other patients.
Conclusions: The serum UA level was an independent predictor in patients who were hospitalized during an emergent situation for AHF. An elevated serum UA level on admission was associated with the presence of CKD and the use of loop diuretics. These factors were also associated with adverse outcomes in hyperuricemic patients with AHF. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2016.04.013

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

Background: No cardiac biomarkers for detecting acute kidney injury (AKI) on admission in non-surgical intensive care patients have been reported. The aim of the present study is to elucidate the role of cardiac biomarkers for quickly identifying the presence of AKI on admission.
Methods: Data for 1183 patients who underwent the measurement of cardiac biomarkers, including the serum heart-type fatty acid-binding protein (s-HFABP) level, in the emergency department were screened, and 494 nonsurgical intensive care patients were enrolled in this study. Based on the RIFLE classification, which was the ratio of the serum creatinine value recorded on admission to the baseline creatinine value, the patients were assigned to a no-AKI (n = 349) or AKI (Class R [n = 83], Class I [n = 36] and Class F [n = 26]) group on admission. We evaluated the diagnostic value of the s-H-FABP level for detecting AKI and Class I/F. The mid-term prognosis, as all-cause death within 180 days, was also evaluated.
Results: The s-H-FABP levels were significantly higher in the Class F (79.2 [29.9 to 200.3] ng/mL) than in the Class I (41.5 [16.7 to 71.6] ng/mL), the Class R (21.1 [10.2 to 47.9] ng/mL), and no-AKI patients (8.8 [5.4 to 17.7] ng/mL). The most predictive values for detecting AKI were Q2 (odds ratio [OR]: 3.743; 95 % confidence interval [CI]: 1.693-8.274), Q3 (OR: 9.427; 95 % CI: 4.124-21.548), and Q4 (OR: 28.000; 95 % CI: 11.245-69.720), while those for Class I/F were Q3 (OR: 5.155; 95 % CI: 1.030-25.790) and Q4 (OR: 22.978; 95 % CI: 4.814-109.668). The s-HFABP level demonstrating an optimal balance between sensitivity and specificity (70.3 and 72.8 %, respectively; area under the curve: 0.774; 95 % CI: 0.728-0.819) was 15.7 ng/mL for AKI and 20.7 ng/mL for Class I/F (71.0 and 83.1 %, respectively; area under the curve: 0.818; 95 % CI: 0.763-0.873). The prognosis was significantly poorer in the high serum HFABP with AKI group than in the other groups.
Conclusions: The s-H-FABP level is an effective biomarker for detecting AKI in non-surgical intensive care patients.

DOI： 10.1186/s12872-016-0340-1

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1161/CIRCULATIONAHA.116.023432

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypertrophy, fibrosis, and accumulation of misfolded proteins and dysfunctional mitochondria. Macroautophagy (hereafter referred to as autophagy) is a lysosome-dependent bulk degradation mechanism that is essential for intracellular protein and organelle quality control. Autophagy and autophagic flux are generally decreased in aging hearts, and murine autophagy loss-of-function models develop exacerbated cardiac dysfunction that is accompanied by the accumulation of misfolded proteins and dysfunctional organelles. On the contrary, stimulation of autophagy generally improves cardiac function in mouse models of protein aggregation by removing accumulated misfolded proteins, dysfunctional mitochondria, and damaged DNA, thereby improving the overall cellular environment and alleviating aging-associated pathology in the heart. Increasing lines of evidence suggest that autophagy is required for many mechanisms that mediate lifespan extension, such as caloric restriction, in various organisms. These results raise the exciting possibility that autophagy may play an important role in combating the adverse effects of aging in the heart. In this review, we discuss the role of autophagy in the heart during aging, how autophagy alleviates age-dependent changes in the heart, and how the level of autophagy in the aging heart can be restored.

DOI： 10.1161/CIRCRESAHA.116.307474

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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：LIPPINCOTT WILLIAMS & WILKINS  

Background- Mitochondrial autophagy is an important mediator of mitochondrial quality control in cardiomyocytes. The occurrence of mitochondrial autophagy and its significance during cardiac hypertrophy are not well understood. Methods and Results- Mice were subjected to transverse aortic constriction (TAC) and observed at multiple time points up to 30 days. Cardiac hypertrophy developed after 5 days, the ejection fraction was reduced after 14 days, and heart failure was observed 30 days after TAC. General autophagy was upregulated between 1 and 12 hours after TAC but was downregulated below physiological levels 5 days after TAC. Mitochondrial autophagy, evaluated by electron microscopy, mitochondrial content, and Keima with mitochondrial localization signal, was transiently activated at approximate to 3 to 7 days post-TAC, coinciding with mitochondrial translocation of Drp1. However, it was downregulated thereafter, followed by mitochondrial dysfunction. Haploinsufficiency of Drp1 abolished mitochondrial autophagy and exacerbated the development of both mitochondrial dysfunction and heart failure after TAC. Injection of Tat-Beclin 1, a potent inducer of autophagy, but not control peptide, on day 7 after TAC, partially rescued mitochondrial autophagy and attenuated mitochondrial dysfunction and heart failure induced by overload. Haploinsufficiency of either drp1 or beclin 1 prevented the rescue by Tat-Beclin 1, suggesting that its effect is mediated in part through autophagy, including mitochondrial autophagy. Conclusions- Mitochondrial autophagy is transiently activated and then downregulated in the mouse heart in response to pressure overload. Downregulation of mitochondrial autophagy plays an important role in mediating the development of mitochondrial dysfunction and heart failure, whereas restoration of mitochondrial autophagy attenuates dysfunction in the heart during pressure overload.

DOI： 10.1161/CIRCULATIONAHA.115.020502

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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：SPRINGER  

This case report describes a patient who underwent implantation of a bare-metal stent (BMS) for the treatment of everolimus-eluting stent (EES) restenosis caused by chronic stent recoil, and the BMS successfully escaped from duplicate restenosis and target lesion revascularization (TLR).

DOI： 10.1007/s00380-014-0588-2

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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 SCI LTD  

Mitochondrial autophagy plays an important role in mediating mitochondrial quality control. Evaluating the extent of mitochondrial autophagy is challenging in the adult heart in vivo. Keima is a fluorescent protein that emits different colored signals at acidic and neutral pHs. Keima targeted to mitochondria (Mito-Keima) is useful in evaluating the extent of mitochondrial autophagy in cardiomyocytes in vitro. In order to evaluate the level of mitochondrial autophagy in the heart in vivo, we generated adeno-associated virus (AAV) serotype 9 harboring either Mito-Keima or Lamp1-YFP.AAV9-Mito-Keima and AAV9-Lamp1-YFP were administered intravenously and mice were subjected to either forty-eight hours of fasting or normal chow. Thin slices of the heart prepared within cold PBS were subjected to confocal microscopic analyses. The acidic dots Mito-Keima elicited by 561 nm excitation were co-localized with Lamp1-YFP dots (Pearson's correlation, 0.760, p &lt; 0.001), confirming that the acidic dots of Mito-Keima were localized in lysosomes. The area co-occupied by Mito-Keima puncta with 561 nm excitation and Lamp1-YFP was significantly greater 48 h after fasting. Electron microscopic analyses indicated that autophagosomes containing only mitochondria were observed in the heart after fasting. The mitochondrial DNA content and the level of COX1/GAPDH, indicators of mitochondrial mass, were significantly smaller in the fasting group than in the control group, consistent with the notion that lysosomal degradation of mitochondria is stimulated after fasting. In summary, the level of mitochondrial autophagy in the adult heart can be evaluated with intravenous injection of AAV-Mito-Keima and AAV-Lamp1-YFP and confocal microscopic analyses. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.yjmcc.2016.02.007

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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：KARGER  

Objectives: The present study sought to clarify the relationship between matrix metalloproteinase-9 (MMP-9) levels and plaque morphology demonstrated by optical coherence tomography (OCT), and to examine their prognostic impacts in patients with acute coronary syndrome (ACS). Methods: MMP-9 levels were measured for patients with ACS (n = 249). Among 249 patients, 120 with evaluable OCT images were categorized into patients with ruptured plaques (n = 65) and those with nonruptured plaques (n = 55) on the basis of culprit lesion plaque morphology demonstrated by OCT. Results: MMP-9 levels on admission were significantly higher in the rupture group than in the nonrupture group (p = 0.029). Although creatine kinase-MB (CK-MB) on admission was comparable between the groups, peak CK-MB was higher in the rupture group than in the nonrupture group (p &lt; 0.001). By receiver operating characteristic curve analysis, the optimal cut-off value of MMP-9 to detect ruptured plaques was 65.5 ng/ml (p = 0.029). There was a nonstatistically significant trend toward increased cardiac death at 2 years (5.9 vs. 1.0%, p = 0.059) in patients with high MMP-9 ng/ml) compared to those with low MMP-9 (&lt;65.5 ng/ml). Conclusions: MMP-9 can differentiate ACS with ruptured plaques from nonruptured plaques, and MMP-9 may be a valuable predictor of long-term cardiac mortality in patients with ACS reflecting plaque rupture. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000445994

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記述言語：日本語   出版者・発行元：一般社団法人 日本集中治療医学会  

冠動脈自然解離は冠動脈造影での内膜亀裂によるフラップや偽腔の存在により診断されてきた。今回，光干渉断層法で解離腔を明瞭に観察しえた2例を経験した。症例1は冠危険因子のない50歳，女性（非ST上昇型急性冠症候群）。冠動脈造影で右冠動脈中間部に高度狭窄を認め，血管内超音波では全周性冠動脈血腫を確認した。光干渉断層法で中膜外膜間に解離腔を認め，冠動脈自然解離と診断した。症例2は喫煙歴のある42歳，女性（ST上昇型急性冠症候群）。冠動脈造影で左前下行枝に内腔平滑な狭窄（#6，#7：90％，#8：90％）を認めた。光干渉断層法で全周性に解離腔を認め，冠動脈自然解離と診断した。2例とも冠動脈造影で内膜亀裂によるフラップを認めず，動脈硬化性変化に乏しい狭窄病変であった。冠動脈造影のみでは見逃しやすい冠動脈自然解離を，血管内超音波と光干渉断層法により詳細に把握できたので報告する。

DOI： 10.3918/jsicm.23.154

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その他リンク： http://search.jamas.or.jp/link/ui/2016229198

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

Rationale: In Drosophila, the Hippo signaling pathway negatively regulates organ size by suppressing cell proliferation and survival through the inhibition of Yorkie, a transcriptional cofactor. Yes-associated protein (YAP), the mammalian homolog of Yorkie, promotes cardiomyocyte growth and survival in postnatal hearts. However, the underlying mechanism responsible for the beneficial effect of YAP in cardiomyocytes remains unclear.
Objectives: We investigated whether miR-206, a microRNA known to promote hypertrophy in skeletal muscle, mediates the effect of YAP on promotion of survival and hypertrophy in cardiomyocytes.
Methods and Results: Microarray analysis indicated that YAP increased miR-206 expression in cardiomyocytes. Increased miR-206 expression induced cardiac hypertrophy and inhibited cell death in cultured cardiomyocytes, similar to that of YAP. Downregulation of endogenous miR-206 in cardiomyocytes attenuated YAP-induced cardiac hypertrophy and survival, suggesting that miR-206 plays a critical role in mediating YAP function. Cardiac-specific overexpression of miR-206 in mice induced hypertrophy and protected the heart from ischemia/reperfusion injury, whereas suppression of miR-206 exacerbated ischemia/reperfusion injury and prevented pressure overload-induced cardiac hypertrophy. miR-206 negatively regulates Forkhead box protein P1 expression in cardiomyocytes and overexpression of Forkhead box protein P1 attenuated miR-206-induced cardiac hypertrophy and survival, suggesting that Forkhead box protein P1 is a functional target of miR-206.
Conclusions: YAP increases the abundance of miR-206, which in turn plays an essential role in mediating hypertrophy and survival by silencing Forkhead box protein P1 in cardiomyocytes.

DOI： 10.1161/CIRCRESAHA.115.306624

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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：MEDICAL ASSOC NIPPON MEDICAL SCH  

A 70-year-old woman who had been treated for bipolar disorder and dementia was admitted to the intensive care unit of a university hospital with severe dyspnea; pulmonary arterial hypertension was diagnosed after cardiac catheterization was performed. Computed tomography pulmonary angiography showed typical signs of chronic thrombosis in the proximal pulmonary artery without an adequate amount of fresh thrombi, which appeared to be the cause of the elevation in pulmonary artery pressure, and resulted in severe hypoxemia. Therefore, the pulmonary arterial hypertension was classified as belonging to the chronic thromboembolic pulmonary hypertension subgroup. Although the patient's respiratory condition was classified as World Health Organization class IV, she was treated with the combination of oral ambrisentan and tadalafil, rather than intravenous epoprostenol, which she was unable to tolerate. Consequently, both her symptom and hemodynamic status showed rapid improvement with only oral pulmonary vasodilators. This case demonstrates the efficacy of oral treatment alone in elderly patients with severe chronic thromboembolic pulmonary hypertension.

DOI： 10.1272/jnms.82.206

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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：SPRINGER  

There have been few reports discussing the clinical significance of the season of admission of acute heart failure (AHF) patients. The data of 661 patients with AHF admitted to the intensive care unit were analyzed. Patients were assigned to a summer admission (Group-S, n = 113, between July and September), a winter admission (Group-W, n = 214, between December and February), or to the other seasons admission group (Group-O, n = 334). We evaluated the relationships between the seasonal variations and the clinical profiles, and the long-term prognosis. There were significantly more patients with cardiomyopathy and New York Heart Association class 4, and the serum levels of total bilirubin were significantly higher in Group-S (85.8, 24.8 %, and 0.60 [0.50-0.90]) than in Group-W (75.2, 15.4 %, and 0.60 [0.40-0.78]). The left ventricular ejection fraction on admission was significantly reduced and intravenous administration of dobutamine was used more frequently in Group-S (30.0 [25.0-46.0], 31.9 %) than in Group-W (34.4 [25.2-48.0], 20.6 %) and Group-O (35.0 [25.0-46.0], 19.8 %). The multivariate Cox regression model found that summer admission was independently associated with cardiovascular death (HR: 1.58, 95 % CI 1.01-2.48; p = 0.044) and heart failure (HF) events (HR: 1.55, 95 % CI 1.05-2.28; p = 0.028). The Kaplan-Meier curves showed that the cardiovascular death rate was significantly higher in Group-S than in Group-W and Group-O, and the HF events were significantly higher in Group-S than in Group-O. The summer admission AHF patients included sicker patients, and the prognosis in these patients was worse than in the patients admitted at other times.

DOI： 10.1007/s00380-013-0461-8

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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 SOC  

Background: Different mechanisms of acute kidney injury (AKI) may exist for acute heart failure (AHF) patients compared with other patients.
Methods and Results: We analyzed data from 282 patients with AHF. The biomarkers were measured within 30 min of admission. Patients were assigned to a no-AKI (n=213) or AKI group (Class R (n=49), Class I (n=15) or Class F (n=5)) using the RIFLE classifications on admission. We evaluated the relationships between the biomarkers and AKI, in-hospital mortality, all-cause death and HF events (HF re-admission, all-cause death) within 90 days. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the AKI than in the no-AKI group, and the predictive biomarker for AKI was s-HFABP (odds ratio: 6.709; 95% confidence interval: 3.362-13.391). s-HFABP demonstrated an optimal balance between sensitivity and specificity (71.0%, 79.3%; area under the receiver-operating characteristic curve [AUC]=0.790) at 22.8 ng/ml for AKI, at 22.8 ng/ml for Class I/F (90.0%, 71.4%; AUC=0.836) and at 21.0 ng/ml for in-hospital mortality (74.3%, 70.0%; AUC=0.726). The Kaplan-Meier survival curves showed a significantly poorer prognosis in the high s-HFABP group (&gt;= 22.9 ng/ml) than in other groups.
Conclusions: The s-HFABP level can indicate AKI on admission, and a high s-HFABP level is associated with a poorer prognosis for AHF patients.

DOI： 10.1253/circj.CJ-14-0653

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記述言語：英語   出版者・発行元：ELSEVIER SCI LTD  

Mitochondria are essential organelles that produce the cellular energy source, ATP. Dysfunctional mitochondria are involved in the pathophysiology of heart disease, which is associated with reduced levels of ATP and excessive production of reactive oxygen species. Mitochondria are dynamic organelles that change their morphology through fission and fusion in order to maintain their function. Fusion connects neighboring depolarized mitochondria and mixes their contents to maintain membrane potential. In contrast, fission segregates damaged mitochondria from intact ones, where the damaged part of mitochondria is subjected to mitophagy whereas the intact part to fusion. It is generally believed that mitochondrial fusion is beneficial for the heart, especially under stress conditions, because it consolidates the mitochondria's ability to supply energy. However, both excessive fusion and insufficient fission disrupt the mitochondrial quality control mechanism and potentiate cell death. In this review, we discuss the role of mitochondrial dynamics and mitophagy in the heart and the cardiomyocytes therein, with a focus on their roles in cardiovascular disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". (C) 2014 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.yjmcc.2014.09.019

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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：LIPPINCOTT WILLIAMS & WILKINS  

Rationale: Both fusion and fission contribute to mitochondrial quality control. How unopposed fusion affects survival of cardiomyocytes and left ventricular function in the heart is poorly understood.
Objective: We investigated the role of dynamin-related protein 1 (Drp1), a GTPase that mediates mitochondrial fission, in mediating mitochondrial autophagy, ventricular function, and stress resistance in the heart.
Methods and Results: Drp1 downregulation induced mitochondrial elongation, accumulation of damaged mitochondria, and increased apoptosis in cardiomyocytes at baseline. Drp1 downregulation also suppressed autophagosome formation and autophagic flux at baseline and in response to glucose deprivation in cardiomyocytes. The lack of lysosomal translocation of mitochondrially targeted Keima indicates that Drp1 downregulation suppressed mitochondrial autophagy. Mitochondrial elongation and accumulation of damaged mitochondria were also observed in tamoxifen-inducible cardiac-specific Drp1 knockout mice. After Drp1 downregulation, cardiac-specific Drp1 knockout mice developed left ventricular dysfunction, preceded by mitochondrial dysfunction, and died within 13 weeks. Autophagic flux is significantly suppressed in cardiac-specific Drp1 knockout mice. Although left ventricular function in cardiac-specific Drp1 heterozygous knockout mice was normal at 12 weeks of age, left ventricular function decreased more severely after 48 hours of fasting, and the infarct size/area at risk after ischemia/reperfusion was significantly greater in cardiac-specific Drp1 heterozygous knockout than in control mice.
Conclusions: Disruption of Drp1 induces mitochondrial elongation, inhibits mitochondrial autophagy, and causes mitochondrial dysfunction, thereby promoting cardiac dysfunction and increased susceptibility to ischemia/reperfusion.

DOI： 10.1161/CIRCRESAHA.116.303356

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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 SCIENCE BV  

Background: No scoring system for assessing acute heart failure (AHF) has been reported.
Methods and results: Data for 824 AHF patients were analyzed. The subjects were divided into an alive (n =750) and a dead group (n= 74). We constructed a predictive scoring system based on eight significant APACHE II factors in the alive group [mean arterial pressure (MAP), pulse, sodium, potassium, hematocrit, creatinine, age, and Glasgow Coma Scale (GCS); giving each one point], defined as the APACHE-HF score. The patients were assigned to five groups by the APACHE-HF score [Group 1: point 0 (n = 70), Group 2: points 1 and 2 (n =343), Group 3: points 3 and 4 (n =294), Group 4: points 5 and 6 (n =106), and Group 5: points 7 and 8 (n =11)]. A higher optimal balance was observed in the APACHE-HF between sensitivity and specificity [87.8%, 63.9%; area under the curve (AUC)= 0.779] at 2.5 points than in the APACHE II (47.3%, 67.3%; AUC= 0.558) at 17.5 points. The multivariate Cox regression model identified belonging to Group 5 [hazard ratio (HR): 7.764, 95% confidence interval (CI) 1.586-38.009], Group 4 (HR: 6.903, 95%CI 1.940-24.568) or Group 3 (HR: 5.335, 95%CI 1.582-17.994) to be an independent predictor of 3-year mortality. The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and HE events (death, readmission-HE), in Group 5 and Group 4 than in the other groups, in Group 3 than in Group 2 or Group 1, and in Group 2 than in Group 1.
Conclusions: The new scoring system including MAP, pulse, sodium, potassium, hematocrit, creatinine, age, and GCS (APACHE-HF) can be used to predict adverse outcomes of AHF. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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：SPRINGER HEIDELBERG  

Biomarkers predicting adverse outcomes in non-surgical intensive care patients have not been reported.
Data for 1,006 emergency department patients were prospectively analyzed. The serum heart-type fatty acid-binding protein (s-H-FABP) level was measured within 10 min of admission. The patients were assigned to intensive care (n = 835) or other departments (n = 171). The intensive care patients were divided into survivors (n = 745) and non-survivors (n = 90) according to the in-hospital mortality and assigned to four groups according to the quartiles of s-H-FABP (Q1, Q2, Q3 and Q4). The s-H-FABP levels were significantly higher in the intensive care patients (12.7 [6.1-38.8] ng/ml versus 5.3 [3.1-9.4] ng/ml) and in the non-survivors (44.9 [23.2-87.6] ng/ml versus 11.5 [5.6-32.6] ng/ml). A Kaplan-Meier curve showed a significantly higher survival rate in Q3 than in Q1 and Q2 and in Q4 than in the other groups. The multivariate Cox regression model identified Q3 (HR 4.646, 95 % CI 1.526-14.146) and Q4 (HR 9.483, 95 % CI 3.152-28.525) as independent predictors of 90-day mortality. The sensitivity and specificity of H-FABP for in-hospital mortality were 81.1 and 66.0 % (AUC 0.775) at 20.95 ng/ml. The in-hospitality rate was significantly higher in the high s-H-FABP patients than in the low s-H-FABP patients in each etiology group.
The s-H-FABP level is an effective biomarker for risk stratification in non-surgical intensive care patients.

DOI： 10.1007/s00392-014-0717-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：JAPANESE CIRCULATION SOC  

Background: Tolvaptan, an oral selective vasopressin 2 receptor antagonist that acts on the distal nephrons to cause a loss of electrolyte-free water, is rarely used during the acute phase of acute heart failure (AHF).
Methods and Results: We investigated 183 AHF patients admitted to the intensive care unit and administered tolvaptan (7.5 mg) with continuous intravenous furosemide, and then additionally at 12-h intervals until HF was compensated. When intravenous furosemide was changed to peroral use, the administration of tolvaptan was stopped. The patients were assigned to tolvaptan (n=52) or conventional treatment (n=131) groups. The amount of intravenous furosemide was significantly lower (35.4 [16.3-56.0] mg vs. 80.0 [30.4-220.0] mg), the urine volume was significantly higher on days 1 and 2(3,691 [3,109-4,198] ml and 2,953 [2,128-3,592] ml vs. 2,270 [1,535-3,258] ml and 2,129 [1,407-2,906] ml) and the numbers of patients with worsening-AKI (step-up RIFLE Class to I or F) and Class F were significantly fewer (5.8% and 1.9% vs. 19.1% and 16.0%) in the tolvaptan group than in the conventional group, respectively. One of the specific medications indicated worsening-AKI and in-hospital mortality was tolvaptan (odds ratio [OR] 0.155, 95% confidence interval [CI] 0.037-0.657 and OR 0.191, 95% CI 0.037-0.985). The Kaplan-Meier curves showed that the death rate within 6 months was significantly lower in the tolvaptan group. The same result was found after propensity matching of the data.
Conclusions: Early administration of tolvaptan could prevent exacerbation of AKI and improve the prognosis for AHF patients.

DOI： 10.1253/circj.CJ-13-1255

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Complicated respiratory failure requiring mechanical ventilation in patients with type-B acute aortic dissection (AAD) has been previously reported, and inflammatory reactions have been found to be associated with the occurrence of oxygenation impairment (OI). However, the possibility of predicting the occurrence of OI in patients with type-B AAD has not yet been evaluated. This study was performed to investigate the possibility of predicting the occurrence of OI in type-B AAD. In this study, 79 type-B AAD patients were enrolled to investigate the possibility of predicting the occurrence of OI. OI was defined as Po 2/Fio 2 ≤ 200. Patient characteristics, type of AAD, vital signs on admission, and the presence of inflammatory reactions obtained on admission day were evaluated. OI occurred in 39 patients (49%) on hospital day 2.5 ± 1.4 on average. Younger age, male gender, nonslender frame (body mass index ≥ 22 kg/m2), a relatively high maximum body temperature on the admission day (≥ 36.5°C), DeBakey IIIb type, patent false lumen, and lower Po 2/Fio 2 on admission were found to be associated with the occurrence of OI. Multivariate analysis revealed that nonslender frame, relatively high body temperature on the admission day, and lower Po 2/Fio 2 on admission were reliable for predicting the occurrence of oxygen impairment. The occurrence of OI in type-B AAD can be predicted in the clinical setting. Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

DOI： 10.1055/s-0033-1349398

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記述言語：英語   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2013.12.042

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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.jjcc.2013.06.013

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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 IRELAND LTD  

Background: Relationships between plaque morphology on optical coherence tomography (OCT) and biomarker levels in the patients with acute coronary syndrome (ACS) have not been fully investigated.
Methods: ACS patients (n = 128) were prospectively enrolled and their plasma levels of soluble lectin-like oxidized LDL receptor-1 (sLOX-1), high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity troponin T (hs-TnT) were measured. Another set of 20 patients with stable angina pectoris (SAP) without plaque rupture or erosion served as controls. Among 128 ACS patients, 75 patients underwent OCT procedure to evaluate culprit plaque morphology, and were categorized into two groups; ACS with plaque rupture (ruptured ACS; R-ACS, n = 54) and ACS without plaque rupture (non-ruptured ACS; N-ACS, n = 21).
Results: Levels of sLOX-1 (p &lt; 0.001), hs-CRP (p = 0.048) and hs-TnT (p &lt; 0.001) were significantly higher in R-ACS than SAP. Levels of sLOX-1 were also significantly higher in R-ACS than in N-ACS (p &lt; 0.001); whereas levels of hs-CRP (p = 0.675), as well as those of hs-TnT (p = 0.055), were comparable between R-ACS and N-ACS. Comparison of receiver operating characteristic (ROC) curves among sLOX-1, hs-CRP and hs-TnT to differentiate R-ACS from N-ACS revealed that the area under the curve (AUC) values of sLOX-1, hs-CRP and hs-TnT were 0.782, 0.531 and 0.643, respectively. ROC curves, generated for these biomarkers, to differentiate ACS with thin-cap fibroatheroma (TCFA) from those without demonstrated that the AUC values of sLOX-1, hs-CRP and hs-TnT were 0.718, 0.506 and 0.524, respectively.
Conclusion: sLOX-1, but not hs-CRP or hs-TnT, can differentiate ACS with plaque rupture from those without, and ACS with TCFA from those without. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2013.04.110

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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.2013.05.019

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記述言語：英語  

DOI： 10.1136/bcr-2013-009886

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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：MEDICAL ASSOC NIPPON MEDICAL SCH  

Aim of the Study: Cardiopulmonary resuscitation and mild therapeutic hypothermia (MTH) have improved neurological outcomes after sudden cardiac arrest, but the factors affecting favorable neurological outcome remain unclear. The aim of this study was to clarify these factors in patients in cardiac arrest treated with MTH.
Methods: Forty-six consecutive patients (mean age, 59.4 +/- 14.3 years; 37 men and 9 women) who had had cardiogenic cardiac arrest from January 2008 through December 2011, including cases that were and were not shockable, were enrolled in this study, and the factors affecting favorable neurological outcome were retrospectively investigated. The interval from cardiac arrest to cardiopulmonary resuscitation, the return of spontaneous circulation (ROSC), the start of MTH, and the attaining of the target temperature were retrieved from the medical records. The relationship between the neurological outcome and clinical findings, including the causes of cardiac arrest and vital signs before MTH, were also investigated.
Results: Blood pressure and body temperature before MTH were higher, the interval from cardiac arrest to ROSC was shorter, and MTH was started earlier in patients with favorable neurological outcomes than in those with unfavorable outcomes. A multivariate logistic regression model revealed that the presence of prehospital ROSC was predictive of a favorable neurological outcome. In addition, renal failure during MTH occurred more frequently in patients with unfavorable neurological outcomes.
Conclusion: MTH is associated with favorable neurological outcomes after sudden cardiac arrest, including those with non-shockable rhythms, especially in patients with prehospital ROSC.

DOI： 10.1272/jnms.80.287

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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 SOC  

Background: The predictive factors for survival after percutaneous cardiopulmonary support (PCPS) are unknown.
Methods and Results: Data for 105 patients with cardiovascular disease requiring PCPS were analyzed. The patients were divided into a survivor (n=21) or a non-survivor group (n=84). The age was significantly lower, and there were more patients with fulminant myocarditis and PCPS attempted before cardiac arrest (CA) in the survivor group. Additionally, there were fewer cases of out-of-hospital CA, and the mean time from CA to PCPS was shorter in the survivor group. On multivariate logistic regression it was found that the age and the time from CA to PCPS were independently associated with survival. A predictive scoring system was constructed that included the following: (1) age &lt;50 years; (2) diagnosis of fulminant myocarditis; (3) no out-of-hospital CA; (4) PCPS attempted before CA; and (5) time from CA to PCPS &lt;45 min. The predictive score was significantly higher in the survivor than in the non-survivor group (2.33+/-1.32 vs. 1.06+/-1.02). The sensitivity and specificity for survival were 85.7% and 66.7% when the score was &gt;= 2. Kaplan-Meier survival analysis showed that any-cause death was significantly higher in patients with PCPS survival score &lt;= 1 than in those with a score &gt;= 2.
Conclusions: PCPS survival score is suitable for clinically predicting survival in patients with cardiovascular disease undergoing PCPS.

DOI： 10.1253/circj.CJ-12-1326

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掲載種別：研究論文（学術雑誌）  

Aim. The aim of this study is to clarify the clinical significance of acute kidney injury (AKI), evaluated by standard method, in patients with non-surgical type-B acute aortic dissection (AAD). Methods. AKI was evaluated by using the RIFLE (Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease) classification in 94 non-surgical type-B AAD patients. The incidence of AKI during hospitalization, factors associated with the occurrence of AKI, and relationships between AKI and outcomes were analyzed retrospectively. Results. AKI occurred in 59 (62.8%) during hospitalization on hospital day 4.6±5.4. The occurrence of AKI was associated with maximum C-reactive protein, white blood cell count, prolongation of high body temperature, and visceral ischemia including the kidney and the gastrointestinal tract. AKI frequently occurred in non-surgical type-B AAD patients, and it was associated with renal circulation and inflammatory reactions. The renal function recovered in 44% of AKI patients during hospitalization, especially in those without chronic renal insufficiency. The duration of both the stay in the ICU stay and hospital were longer in patients with severe AKI (class F category of AKI) than others. Conclusion. AKI frequently occurred in non-surgical type-B AAD, and it was associated with renal circulation, inflammatory reactions, and poor outcome. And the renal function recovered in 44% of AKI patients during hospitalization, especially in those without chronic renal insufficiency.

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記述言語：英語   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2012.09.158

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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 SOC  

Background: The relationship between acute kidney injury (AKI) in the acute phase of acute decompensated heart failure (ADHF) and patient outcome has not yet been reported.
Methods and Results: Data for 625 patients with ADHF admitted to the intensive care unit were analyzed. No AKI occurred in 281 patients (no AKI) during the first 5 days. The AKI patients were assigned to 3 groups based on the timing: AKI present on admission and stable risk, injury, failure, loss, and endstage (RIFLE) class (stable early AKI; n=125), stepped-up RIFLE class (worsening early AKI; n=49), or AKI that occurred after admission (late AKI; n=170). The AKI patients were grouped into another 3 groups based on severity: class R (risk; n=214), class I (injury; n=73), or class F (failure; n=57). A multivariate logistic regression model found class I, class F, late AKI and worsening early AKI to be independently associated with in-hospital mortality. Kaplan-Meier survival curves showed that the survival rate in any-cause death during 2 years was significantly lower in class I, class F and the worsening early-AKI group, and there were significantly more HF events in class F and the worsening early-AKI group. There were significantly more class I and class F patients in the worsening early-AKI group.
Conclusions: The presence of AKI on admission, worsening of AKI, and severe AKI (class I or class F) are associated with a poorer prognosis for ADHF patients. (Circ J 2013; 77: 687-696)

DOI： 10.1253/circj.CJ-12-0994

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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：AMER DIABETES ASSOC  

OBJECTIVE-To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity.
RESEARCH DESIGN AND METHODS-Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups.
RESULTS-Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs &gt;= 2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09-55.61, P = 0.005; and OR 4.13 [95% CI 1.01-17.01, P = 0.049, respectively).
CONCLUSIONS-Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. Diabetes Care 36:729-733,2013

DOI： 10.2337/dc12-1635

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: There have been few reports about the clinical significance of the time of admission for acute heart failure (AHF). Methods: Five hundred thirty-one patients with AHF admitted to the intensive care unit (ICU) were analyzed. The patients were assigned to either the daytime HF group (n=195, visited from 08:00 to 20:00, Group D) or nighttime HF group (n=336, visited from 20:00 to 08:00, Group N). The clinical findings and outcomes were compared between these groups. Results: The systolic blood pressure (SBP), the number of patients with clinical scenario (CS) 1, and the heart rate (HR) were significantly higher in group N (SBP, 171.0 ± 38.9. mmHg
CS 1, 80.9%
HR, 116.9 ± 28.0. beats/min) than in group D (SBP, 154.2 ± 37.1. mmHg
CS 1, 66.2%
HR, 108.6 ± 31.4. beats/min). The patients in group N were more likely to have orthopnea (91.1%) than those in group D (70.3%). A multivariate logistic regression model identified a SBP ≥164. mmHg [odds ratio (OR): 2.043
95% confidence interval (CI): 1.383-3.109], HR ≥114. beats/min (OR: 1.490
95%CI: 1.001-2.218), and orthopnea (OR: 2.257
95%CI: 1.377-3.701) to be independently associated with Group N. The length of ICU stay was shorter in group N (5.8 ± 10.5 days) than in group D (7.8 ± 11.5 days). Conclusion: The nighttime HF was characterized by high SBP, high HR, and orthopnea, and the length of ICU stay was shorter in the nighttime HF group. © 2012 Japanese College of Cardiology.

DOI： 10.1016/j.jjcc.2012.10.004

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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 SOC  

Background: Although coronary vasospasm (CVS) would be one of the major causes of out-of-hospital cardiac arrest (OHCA), the characteristics of patients with cardiac arrest caused by CVS have not been clarified.
Methods and Results: In study 1, 1,000 consecutive patients with OHCA were retrospectively categorized based on the cause of OHCA, and the prevalence of CVS OHCA was elucidated. In study 2, 138 consecutive CVS patients were divided into 2 groups: CVS with cardiac arrest (arrest-CVS, n=12) and CVS without cardiac arrest (non-arrest-CVS, n=126). In study 1, 589 patients had OHCA caused by cardiovascular disease and 121 patients were successfully resuscitated. Among the 121 resuscitated patients, 9 had CVS OHCA. In study 2, the incidence of cardiac events (le, cardiac arrest or chest pain) occurring on vigorous exertion, in the daytime and without prodromal chest symptoms was higher in the arrest-CVS group than in the non-arrest-CVS group.
Conclusions: CVS is an important cause of OHCA. Because significantly different characteristics are observed between CVS patients with cardiac arrest and those without, care should be taken to diagnose CVS as the cause of cardiac arrest. (Circ J 2013;77: 673-678)

DOI： 10.1253/circj.CJ-12-0846

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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.2012.05.062

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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.2012.09.001

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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：INT HEART JOURNAL ASSOC  

The relationship between the short-term prognosis of acute heart failure (AHF) and acute kidney injury (AKI) using the risk, injury, failure, and end stage (RIFLE) criteria has already been reported, however, the relationship between the long-term prognosis and AKI has not. We investigated the relationship between the long-term prognosis after discharge and AKI using the RIFLE criteria. Five hundred patients with AHF admitted to our intensive care unit were analyzed. Patients were assigned to a no AKI (n = 156), Class R (risk; n = 201), Class I (injury; n = 73), or Class F (failure; n = 70) using the most severe RIFLE classifications during hospitalization. We evaluated the relationships between the RIFLE classifications and any-cause death, and HF events including death and readmission for I-IF within I year. A multivariate logistic regression model found that Class I (P = 0.013, OR: 2.768; 95% CI: 1.236-6.199) and Class F (P &lt; 0.001, OR: 7.920; 95% CI: 3.497-17.938) were independently associated with any-cause death, and Class F was associated with HF events (P = 0.001, OR: 3.486; 95% CI: 1.669-7.281). The Kaplan-Meier survival curves showed the prognosis, including death, to be significantly poorer in Class I than in no AKI and Class R, to be significantly poorer in Class F than in no AM, Class R, and Class I, and the prognosis including HF events to be significantly poorer in Class F than in no AKI, Class R, and Class I. The presence of severe AKI (Class I and F) was independently associated with long-term mortality for AHF. (lilt Heart J 2012; 53: 313-319)

DOI： 10.1536/ihj.53.313

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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 SCIENCE BV  

Background and purpose: The role of an arterial blood gas analysis in acute heart failure (AHF) remains unclear. The acid-base balance could help to treat AHF, and it might help to distinguish different types of AHF, while it might be associated with the AHF prognosis. The present study was conducted to determine the relationship between the arterial blood gas sample at the time of hospital admission and clinical findings on admission, outcomes.
Methods and results: Six hundred twenty-one patients with AHF admitted to the intensive care unit were analyzed. Patients were assigned to an alkalosis group (n = 99, pH &gt; 7.45), normal group (n = 178, 7.35 &lt;= pH &lt;= 7.45), and acidosis group (n = 344, pH &lt; 7.35). The clinical findings on admission and outcomes (in-hospital mortality and any-cause death within 2 years) were compared between the three groups. The white blood cell counts (WBC), serum levels of total protein, albumin, and glucose were significantly lower, and the serum levels of C-reactive protein (CRP) and total bilirubin were significantly higher in the alkalosis group. Patients with orthopnea were significantly fewer, and the systolic blood pressure (SBP) and heart rate (HR) were significantly lower in the alkalosis group. The results of a multivariate logistic regression model for in-hospital mortality found that alkalosis was an independent risk factor (p = 0.017, odds ratio: 2.589; 95% confidence interval: 1.186-5.648). The Kaplan-Meier curves showed the prognosis for any-cause death to be significantly poorer in the alkalosis group than in the normal group (p = 0.026).
Conclusions: The factors associated with alkalosis AHF were high CRP, bilirubin, and low WBC, glucose, total protein, and albumin. The patients with alkalosis AHF were less likely to have orthopnea with low SBP and HR. They suggested that the patients with alkalosis AHF might have experienced AHF for a few days and were associated with high mortality. (C) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2012.06.004

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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 IRELAND LTD  

Background and purpose: We have reported that matrix metalloproteinase-2 (MMP-2) increased in acute heart failure (AHF) and better prognosis was found in patients with greater reduction in MMP-2. We assessed whether a statin decreased MMP-2 in AHF.
Methods and results: The serum MMP-2 levels were measured on admission (Day 1), Day 3, Day 7, and Day 14 in 50 AHF patients. The patients were randomized to either atorvastatin (n=25) or control group (n=25). Atorvastatin (10-20 mg/day) was started within 12h after their admission and then was continued for two weeks. There were no differences in the serum levels of MMP-2 on Day 1 between atorvastatin group (1400.4 +/- 318.6 ng/ml) and control group (1292.7 +/- 384.7 ng/ml). MMP-2 significantly decreased in both groups on Day 3, 7, and 14. However, the MMP-2 value on Day 3 compared to Day 1 was observed to have decreased significantly in atorvastatin group (561.8 +/- 235.1 ng/ml) compared to control group (272.6 +/- 270.6 ng/ml; p = 0.001). HF events which were defined as death from HF, readmission to hospital for HE or prolonged hospital stay because of uncontrollable HF, occurred more in control group than in atorvastatin group. Kaplan-Meier curves showed that the prognosis of HF was significantly better in atorvastatin group as compared with control group (log-rank test, p = 0.037).
Conclusion: In addition to conventional HF therapy, an early start of atorvastatin caused a great decrease in MMP-2 and also improved HF events in AHF. (C) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2012.01.009

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

DOI： 10.1016/j.jacc.2011.07.063

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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 SOC  

Background: Matrix metalloproteinase-9 (MMP-9) is regarded as a biomarker of plaque rupture or vulnerability and is elevated in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate the diagnostic value of MMP-9 for early ACS (&lt;= 4h of onset) and late ACS (&gt;4h after onset), compared with high-sensitivity troponin T (hs-TnT).
Methods and Results: MMP-9 and hs-TnT were measured in 200 patients with ST elevation ACS (STEACS; 115 early STEACS and 85 late STEACS patients), and 66 patients with non-ST elevation ACS (NSTEACS; 25 early NSTEACS and 41 late NSTEACS patients). Forty patients with stable angina pectoris (SAP) were enrolled as a control group. MMP-9 levels were significantly higher in patients with early STEACS (P&lt;0.001), early NSTEACS (P&lt;0.001), late STEACS (P&lt;0.001) and late NSTEACS (P=0.025) than SAP. MMP-9 levels were significantly higher in patients with early STEACS (P=0.017) and early NSTEACS (P=0.034) than late STEACS and late NSTEACS, respectively. Levels of hs-TnT were significantly lower in patients with early STEACS (P&lt;0.001) and early NSTEACS (P=0.007) than late STEACS and late NSTEACS, respectively. On receiver operating characteristic curve analysis, area under the curve of early STEACS, early NSTEACS, late STEACS and late NSTEACS was 0.880, 0.782, 0.790 and 0.648 for MMP-9, and 0.707, 0.725, 0.993 and 0.920 for hs-TnT, respectively.
Conclusions: MMP-9 levels were elevated earlier than hs-TnT and had a higher diagnostic value for early ACS, but not for late ACS, reflecting plaque rupture or vulnerability. (Circ J 2011; 75: 2853-2861)

DOI： 10.1253/circj.CJ-11-0640

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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 SOC  

Background: Although highly sensitive assays for troponin T (hs-TnT) have been developed, the sensitivity and specificity of hs-TnT for diagnosing acute coronary syndrome (ACS) remains imperfect. We evaluated the diagnostic value of a new biomarker of plaque vulnerability (soluble lectin-like oxidized low-density lipoprotein receptor-1, sLOX-1) as compared with hs-TnT in the emergency room (ER).
Methods and Results: Plasma sLOX-1 and serum hs-TnT levels were measured in 200 consecutive patients presenting with chest symptoms and ECG abnormalities in the ER (116 ST elevation ACS [STEACS], 44 non-ST elevation ACS [NSTEACS], 40 non-ACS). The non-ACS group consisted of patients with cardiovascular diseases such as coronary spastic angina pectoris, pulmonary thromboembolism, perimyocarditis and takotsubo cardiomyopathy. Levels of sLOX-1 and hs-TnT were significantly higher in STEACS and NSTEACS than in non-ACS patients. The receiver-operating characteristic (ROC) curves of sLOX-1 and hs-TnT for detecting ACS, using the non-ACS patients as negative references, showed that the area under the curve (AUC) values of sLOX-1 and hs-TnT were 0.769 and 0.739, respectively. In the lower hs-TnT (&lt;0.0205 ng/ml) subgroup, the AUC value of the ROC curve of sLOX-1 for detecting ACS was 0.869.
Conclusions: The diagnostic value for ACS was comparable between sLOX-1 and hs-TnT, and the accuracy of ACS diagnosis appeared to improve when sLOX-1 and hs-TnT were measured in combination. (Circ J 2011; 75: 2862-2871)

DOI： 10.1253/circj.CJ-11-0724

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although helicopters have been used in an air ambulance system for the past decade in Japan, the appropriate selection of patients for this transport mode has not been investigated. The present study investigates which patients could potentially benefit the most from helicopter emergency medical service (HEMS). We investigated the extent of circulatory and respiratory support required in the intensive care unit (ICU) and ultimate outcomes of 2340 patients with cardiovascular disease admitted to 1 institution between October 2001 and December 2009. Two hundred and seventy were transported by HEMS (HEMS group), and 2070 were transported by other means (non-HEMS group). Temporary cardiac pacing, ventilator management, intra-aortic balloon pumping, percutaneous cardiopulmonary support, electrical defibrillation, and therapeutic hypothermia were more frequently required by patients in the HEMS group vs. the non-HEMS group (10.4, 28.1, 17.0, 5.2, 10.0 and 3.4 vs. 8, 17.9, 10.9, 2.3, 4.5 and 0.4, respectively). The mortality rate was higher in the HEMS group than in the non-HEMS group in the ICU (9.6 vs. 5.3). Disease was more clinically severe and the outcome was poorer among patients with cardiovascular diseases transported by HEMS than by other means. © 2011 Air Medical Journal Associates.

DOI： 10.1016/j.amj.2011.05.004

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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 IRELAND LTD  

Background: Although in-stent restenosis (ISR) after bare-metal stent (BMS) implantation is considered to be clinically benign, ISR is often associated with adverse complications, such as acute coronary syndrome (ACS). The frequency, type, and location of thrombi in ISR lesions and their clinical presentation have not yet been precisely validated.
Methods: Thirty angiographic ISR lesions occurring within 3 to 8 months after stenting were evaluated by optical coherence tomography (OCT). A thrombus was defined as a mass protruding into the lumen with an irregular surface, and its type was divided into red or white. The maximum size of a thrombus and the longitudinal distance from the thrombus to the narrowest lumen were measured.
Results: A thrombus was identified in 2 patients by angiography and in 10 patients by OCT (7% vs. 33%; P=0.01). OCT showed that 9 patients had white thrombus and another patient had both types of thrombi. ACS relevant to ISR was seen in 6 patients, and the frequency of ACS was significantly higher in patients with thrombus than in those without thrombus [50% (5/10) vs. 5% (1/20); P=0.003]. The maximum size of the thrombus was 412 +/- 220 mu m in height, 424 +/- 251 mu m in width, and the longitudinal distance between the thrombus and the minimum lumen area was 0.3 +/- 0.7 mm.
Conclusions: One third of ISR lesions following BMS deployment dominantly contained a white thrombus, and half of them were associated with ACS. A small thrombus formation adjacent to the narrowest lumen in an ISR lesion may therefore contribute to the clinical presentation of ACS. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2009.12.027

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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 IRELAND LTD  

Background: Non-invasive positive pressure ventilation (NPPV) for acute heart failure (AHF) is increasingly used to avoid endotracheal intubation (ETI). We therefore reviewed our experience using respirator management in the emergency room for AHF, and evaluated the predictive factors in the success of NPPV in the emergency room.
Methods and results: Three-hundred forty-three patients with AHF were analyzed. The AHF patients were assigned to either BiPAP-Synchrony (R) (B-S; Respironics, Merrysville, PA, USA) period (2005-2007, n = 176) or BiPAP-Vision (R) (B-V; Respironics) period (2008-2010, n = 167). The rate of carperitide use was significantly increased and dopamine use was significantly decreased in the B-V period. The total length of hospital stay was significantly shorter in the B-V period. AHF patients were also assigned to a failed trial of NPPV followed by ETI (NPPV failure group) or an NPPV success group in the emergency room for each period. NPPV was successfully used in 48 cases in the B-S period, and in 111 cases in the B-V period. Fifty-seven ETI patients included 45 direct ETI and 11 NPPV failure cases in the B-S period, and 16 ETI patients included 10 direct ETI and 6 NPPV failure cases in the B-V period. The pH values were significantly lower in the NPPV failure than in the NPPV success for both periods (7.19 +/- 0.10 vs. 7.28 +/- 0.11, B-S period, p &lt; 0.05; 7.05 +/- 0.08 vs. 7.27 +/- 0.14, B-V period, p &lt; 0.001). A pH value of 7.20 produced the optimal balance in the B-S period, while that of 7.03 produced the optimal balance in B-V periods by the ROC curve analysis. The cutoff value of pH was lower in the B-V period than in the B-S period.
Conclusions: This predictive value provides successful estimates of NPPV with a high sensitivity and specificity, and the aortic blood gas level was above 7.03 pH when using the B-V system. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2010.10.004

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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：SPRINGER  

The serum levels of matrix metalloproteinases (MMPs) increase during chronic heart failure (HF) and the MMP-2 are related to a poor prognosis. However, the roles of MMP-2 in acute HF (AHF) remain unclear. We investigated the change and clinical significance of MMP-2 in these conditions. The serum levels of MMP-2 were measured in 83 AHF patients before starting treatment (day 1), 3 (day 3) and 7 (day 7) days after admission, and before discharge (predischarge). MMP-2 decreased rapidly and significantly from day 3 to day 1 (902.9 +/- 304.2 versus 1220.4 +/- 330.5 ng/mL; P &lt; 0.0001), whereas that of MMP-2 was not significantly different on day 7 and at predischarge (894.7 +/- 278.9 and 920.0 +/- 269.6 ng/mL, respectively) compared to day 3. We evaluated the relationships between Delta MMPs, defined as the changes in MMPs from day I to day 3 and HF events including cardiac death, readmission to hospital for HF, and uncontrollable HF. The MMP-2 value was significantly (P = 0.004) more decreased in the event-free group (381.4 +/- 256.5 ng/mL) than in the event group (211.9 +/- 225.5 ng/mL) between clay I and day 3. The results of the multivariate logistic regression model for predicting HF events found that the specific factor for HF events was Delta MMP-2. Cutoff values of Delta MMP-2 were determined and event-free curves were constructed. Kaplan-Meier curves showed that the prognosis was significantly better among the patients with reductions in Delta MMP-2 values of more than 342 ng/mL. The serum levels of MMP-2 decreased with improvements in AHF. Rapid decreases in MMP-2 may be important for a better clinical outcome in patients with NU. (Int Heart J 2010; 51: 404-410)

DOI： 10.1536/ihj.51.404

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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 IRELAND LTD  

Background: Nicorandil is a vasodilator that both opens potassium channels and has nitrate effects. The administration of nitrate is the gold standard for the treatment of acute heart failure (AHF). However, there have been few reports regarding the usefulness of nicorandil for the treatment of AHF. Therefore, we evaluated the efficacy of intravenous administration of nicorandil in patients with AHF.
Methods: A total of 31 AHF patients were enrolled, and randomized into either the nicorandil group (n=16) or control group (n=15). Nicorandil was started with a bolus injection of 100 mu/kg, and the continuous injection of 60-100 mu g/kg/h within 30 min after admission, which continued for 5 days. There were no limitations in the treatment of AHF except for nicorandil use. B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) were measured on admission (Day 1), Day 3, and Day 7.
Results: BNP significantly decreased in the nicorandil group on Day 3 (502.4 +/- 406.9 pg/ml) from Day 1 (1397.0 +/- 1617.5 pg/ml), however, no significant decrease was observed in the control group. NT-pro-BNP tended to decrease on Day 3 (7316.7 +/- 10,187.5 pg/ml, p = 0.06) and significantly decreased on Day 7 (5702.9 +/- 6468.8 pg/ml) from Day 1 (11,270.0 +/- 12,388.5 pg/ml) in the nicorandil group, however there were no changes in the control group. When patients from nicorandil group were classified into a high systolic blood pressure (SBP) group (baseline SBP &gt;140 mm Hg, n=10) and low SBP group (baseline SBP &lt;140 mm Hg, n=6), a significant decrease was observed in SBP from Day 1 to Day 3 in both groups.
Conclusions: Intravenous administration of nicorandil can decrease serum cardiac stress markers, and was shown to be effective in AHF patients. Furthermore, nicorandil improved the hemodynamics in the patients with high SBP, and the drug could be safely administered to AHF patients with low SBP. (C) 2010 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

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）   出版者・発行元：OXFORD UNIV PRESS  

Aims The clinical course including the outcome of acute decompensated heart failure (ADHF) correlates with renal dysfunction, but the evaluation of renal function has not yet been standardized. We therefore investigated the relationship between the prognosis of ADHF and acute kidney injury (AKI) evaluated using the risk, injury, failure, loss, end stage (RIFLE) criteria.
Methods and results This study assessed 376 consecutive patients with ADHF admitted to the intensive care unit (ICU) (mean age 71.6 years; 238 male). The underlying aetiology was ischaemic heart disease, hypertensive heart disease, cardiomyopathy, valvular diseases, and &apos;other&apos; in 124, 70, 60, 107, and 15 patients, respectively. We defined AKI according to the RIFLE criteria, and the most severe RIFLE classifications during hospitalization were adopted to assess patient outcomes. The in-hospital mortality was significantly higher among patients with AKI (29 of 275; 10.5%) than in those without AKI (1 of 101; 1.0%, P = 0.0010). Both ICU and hospital stays were longer for patients with AKI (8.8 +/- 15.4 vs. 48.6 +/- 47.6 days), than for patients without (5.0 +/- 2.8 vs. 25.7 +/- 16.8 days, P &lt; 0.05 and P &lt; 0.001).
Conclusion Acute kidney injury evaluated by the RIFLE criteria was associated with a poorer outcome for patients with ADHF.

DOI： 10.1093/eurjhf/hfp169

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A case of acute heart failure due to Takotsubo cardiomyopathy induced by 5-fluorouracil is described. Acute heart failure developed during the administration of 5-fluorouracil (5-FU) and levofolinate calcium in a 62-year-old woman who had underwent a Miles operation for rectal adenocarcinoma. Electrocardiography upon admission showed slight ST elevation in leads V1-3. and follow-up electrocardiography on the third hospital day evealed QT interval prolongation and giant negative T waves in leads II, III, aVF, and V1-6. Echocardiography and myocardial scintigraphy showed left ventricular apical ballooning in the acute phase of heart failure, but left ventricular contraction was normal during the recovery phase. Coronary angiography demonstrated normal coronary arteries, and multi-vessel coronary artery vasospasms including microcirculation disorders could be provoked by intracoronary acetylcholine infusion during, but not before, the intravenous administration of levofolinate calcium and 5-FU. The cause of heart failure in this patient, Takotsubo cardiomyopathy induced by multivessel coronary vasospasm including microcirculation disorders only during 5-FU administration, is notable.

DOI： 10.1272/jnms.76.27

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Pleural effusions develop for various reasons in patients admitted to intensive care units (ICUs). To understand why this occurs is important, yet cytokine levels in pleural effusions have rarely been measured from a cardiovascular viewpoint. Objective: To understand the characteristics of pleural cytokines in patients admitted to the ICU. Methods: The subjects were 43 patients with pleural effusion who were admitted to the ICU from June 2001 through March 2006. We divided the patients into transudate (n=23) and exudate (n=20) groups. We measured levels of interleukin (IL)-6. IL-10. and tumor necrosis factor (TNF)-α in pleural effusions and peripheral blood and evaluated their relationships with body temperature, C-reactive protein (CRP) level, and the peripheral white blood cell (WBC) count. Results: Levels of pleural IL-6 were significantly higher and levels of TNF-α tended to be higher in pleural effusions from the exudate than in those from the transudate group (3.350 ± 3.627 vs. 1.677 ± 1,086 pg/m and 6.6 ± 3.4 vs. 4.8 ± 2.6 pg/mL. respectively). However, in both groups levels of IL-10 in pleural effusions were similar to those in serum and levels of IL-6 were significantly higher in pleural effusion than in serum. Serum IL-6 levels correlated with inflammatory markers (CRP and body temperature), whereas cytokines in pleural effusion did not correlate with any of these markers (body temperature. CRP. and WBC). Conclusion: Pleural levels of IL-6 were significantly higher in the exudate group than in the transudate group but did not correlate with serum levels of IL-6 or with systemic inflammatory markers. These findings suggest that pleural IL-6 levels correlate with local lung or pleural inflammation in patients admitted to the ICU.

DOI： 10.1272/jnms.75.262

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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 SOC  

Background Acute aortic dissection (AAD) is a life-threatening cardiovascular disorder that is similar to acute coronary syndrome (ACS), which means differentiating AAD and ACS is sometimes difficult in an emergency.
Methods and Results Specific information from 131 patients with AAD or ACS was analyzed between April 2001 and March 2002. The emergency room AAD (ERAAD) score was defined as the total number of specific indexes for AAD among 15 indexes that were obtainable in the emergency room (Study 1). The clinical applicability of the ERAAD score was also investigated in another 711 patients with AAD or ACS between April 2002 and March 2006 (Study 2). The ERAAD score was based on (1) presence of back pain, (2) mediastinal thoracic ratio &gt;30%, (3) aortic regurgitation and (4) aortic diameter &gt;30mm on ultrasonography in Study 1. The ERAAD score was significantly higher in patients with AAD than with ACS (3.19 +/- 0.83 vs 1.17 +/- 0.99) in Study 2. The sensitivity and specificity for AAD were 93.1% and 77.6%, respectively, when the ERAAD score was &gt;= 3.
Conclusion The ERAAD score enables clinical diagnosis of AAD and correct treatment.

DOI： 10.1253/circj.72.986

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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 IRELAND LTD  

We report a case of a 51- year-old man with transient mid-ventricular ballooning cardiomyopathy. Left ventriculography demonstrated mid- ventricular ballooning and akinesis with hypercontractile apical and basal segments. Iodine- 123- beta-methyl-p-iodophenyl-pentadecanoic acid myocardial scintigraphy showed decreased uptake in the mid-ventricle, corresponding to the mid-ventricular akinetic region. This is the first report of a transient mid-ventricular ballooning cardiomyopathy observed by not only left ventriculography but myocardial scintigraphy. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2007.01.076

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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  

Coronary perforation is an undesirable complication during percutaneous coronary intervention (PCI). We reviewed the cases of overt coronary perforation in our institute and analyzed their clinical backgrounds, the characteristics of the target lesion, management, and clinical outcomes. Between 1991 and 2005, we experienced 12 cases (0.35%) of coronary perforation in a total of 3415 PCI procedures. The perforation occurred during the use of debulking devices in 3 cases, immediately after stenting in 2, immediately after postdilatation of the stenting in 2, and during wiring in 3 cases. Restoration was attempted by long inflation of a balloon in 7 cases, implantation of a covered stent graft in 1, and emergency surgical repair in I case. Subsequent cardiac tamponade occurred in 3 patients who required pericardiocentesis, and I patient died due to congestive heart failure. Administration of protamine was effective in stopping the bleeding in 6 patients, whereas continuation of antiplatelet therapy resulted in no overt rebleeding. Coronary perforation during PCI is a rare complication but is associated with significant morbidity and mortality. Intravenous administration of protamine is effective when it is used in conjunction with nonsurgical devices for initial management of perforation.

DOI： 10.1536/ihj.48.1

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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   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1161/CIRCULATIONAHA.116.023667

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(一社)日本集中治療医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：日本心臓病学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2009041245

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：(NPO)日本冠疾患学会  

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記述言語：日本語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：東京医学社  

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その他リンク： http://search.jamas.or.jp/link/ui/2008008726

記述言語：日本語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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