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DOI： 10.1093/ehjci/jeae004

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/ehjcr/ytae025

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Other Link： https://academic.oup.com/ehjcr/article-pdf/8/1/ytae025/56397918/ytae025.pdf

Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1186/s40560-023-00710-2

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

DOI： 10.1016/j.ijcha.2023.101297

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

DOI： 10.1016/j.jacep.2023.08.033

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DOI： 10.1093/ehjci/jead167

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

DOI： 10.1253/circj.CJ-23-0320

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DOI： 10.1016/S0140-6736(23)01675-6

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

DOI： 10.1055/s-0043-1767697

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

DOI： 10.1111/jce.16005

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

DOI： 10.3390/jcm12155137

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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

DOI： 10.1007/s00380-023-02289-y

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

DOI： 10.1186/s40560-023-00676-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

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

DOI： 10.1016/j.jjcc.2023.06.006

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

DOI： 10.1007/s00380-022-02230-9

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Language：English   Publisher：(一社)日本循環器学会  

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

DOI： 10.1002/ehf2.14327

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

DOI： 10.1536/ihj.22-656

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

DOI： 10.1536/ihj.22-572

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

DOI： 10.1536/ihj.22-654

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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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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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：VM Media SP. zo.o VM Group SK  

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

DOI： 10.5603/cj.a2022.0120

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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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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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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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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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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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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DOI： 10.11909/j.issn.1671-5411.2021.10.010

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

DOI： 10.1002/ehf2.13596

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

DOI： 10.1016/j.cardfail.2021.07.022

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

DOI： 10.1007/s13300-021-01103-0

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

DOI： 10.1002/ehf2.13509

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

DOI： 10.1002/ehf2.13489

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DOI： 10.1253/circrep.CR-21-0048

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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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Language：English   Publisher：(一社)日本循環器学会  

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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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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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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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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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

DOI： 10.1253/circrep.CR-20-0132

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1272/jnms.JNMS.2021_88-518

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Peripheral artery disease (PAD), intermittent claudication, and impaired mobility contribute to the loss of skeletal muscle. This study investigated the impact of endovascular treatment (EVT) in patients suffering from PAD above the knee and its relation to baseline glycemic control. METHODS AND RESULTS: Mid-thigh muscle volume was measured before EVT, 3 months after EVT and 6 months after EVT. Mid-thigh muscle volumes of ipsilateral PAD patients with ischemic and non-ischemic legs were compared. Correlations between total thigh muscle volume and clinical characteristics were analyzed using univariable and multivariable analysis. Overall, thigh muscle volume increased after EVT. The mid-thigh muscle volume was significantly lower in patients with ipsilateral lesions and in those with ischemic lower limbs. The thigh muscle volume of those with ischemic lower limbs increased after EVT. Baseline glycated hemoglobin was the only factor that was negatively correlated with changes in the muscle volume after EVT. Muscle volume significantly increased in normoglycemic HbA1c<6.5% (47 mmol/mol) patients. There was no significant alteration in the muscle volume of hyperglycemic HbA1c ≥ 6.5% patients. CONCLUSION: Ischemic muscle atrophy was ameliorated after EVT in normoglycemic patients. There is a need for a large-scale trial to investigate whether EVT can protect or delay skeletal muscle loss.

DOI： 10.1016/j.numecd.2020.09.003

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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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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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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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DOI： 10.4244/EIJ-D-20-00996

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

DOI： 10.1093/ehjcvp/pvaa132

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

DOI： 10.1186/s12933-020-01127-z

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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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Language：English   Publisher：(一社)日本循環器学会  

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Language：English   Publisher：(一社)日本循環器学会  

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/jaha.119.012199

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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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Percutaneous transluminal septal myocardial ablation (PTSMA) has become a significant treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) despite maximal medical therapy. The target septal arteries usually arise from the left anterior descending artery (LAD). However, when septal perforators do not originate from the LAD, non-LAD septal perforators should be included as candidate-target septal branches that feed the hypertrophic septal myocardium, causing left ventricular outflow tract (LVOT) obstruction. Data pertaining to the procedure remain limited. We aimed to investigate PTSMA through the non-LAD septal perforators in patients with HOCM. In this case series review, we evaluated the baseline characteristics, echocardiographic features, and angiographic features, as well as symptoms and pressure gradient before and after PTSMA through the non-LAD septal perforators. Among 202 consecutive patients who underwent PTSMA for HOCM with LVOT obstruction, 21 had non-LAD septal branches that fed the hypertrophic septal myocardium and received alcohol ablation. Non-LAD septal perforators could be used as an alternative route for PTSMA in patients who experienced ineffective ablation of the septal branch that arises from the LAD. This unique procedure may improve response rates and overall outcomes of patients with HOCM.

DOI： 10.1007/s00380-019-01525-8

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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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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

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

DOI： 10.1272/jnms.jnms.2021_88-303

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BACKGROUND: The prognostic impact of hyperuricemia and the factors that induce hyperuricemia in cardiovascular intensive care patients remain unclear. METHODS AND RESULTS: A total of 3257 emergency department patients were screened, and data for 2435 patients who were admitted to an intensive care unit were analyzed. The serum uric acid level was measured within 15 min of admission. The patients were assigned to a low-uric acid group (uric acid ⩽7.0 mg/dl, n=1595) or a high-uric acid group (uric acid >7.0 mg/dl, n=840) according to their uric acid level on admission. Thereafter, the patients were divided into four groups according to the quartiles of their serum uric acid level (Q1, Q2, Q3 and Q4), and uric acid levels and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. A Kaplan-Meier curve showed a significantly lower 365-day survival rate in a high-uric acid group than in a low-uric acid group, and in Q3 than in Q1 or Q2 and in Q4 than in the other groups. The multivariate logistic regression model for 30-day mortality identified Q4 (odds ratio: 1.856, 95% confidence interval (CI) 1.140-3.022; p=0.013) as an independent predictor of 30-day mortality. The area under the receiver-operating characteristic curve values of the serum uric acid level and APACHE II score for the prediction of 30-day mortality were 0.648 and 0.800, respectively. The category-free net reclassification improvement and integrated discrimination improvement showed that the calculated risk shifted to the correct direction by adding the serum uric acid level to the APACHE II score (0.204, 95% CI 0.065-0.344; p=0.004, and 0.015, 95% CI 0.005-0.025; p=0.004, respectively). The prognosis, including the 365-day mortality, among patients with a high uric acid level and a high APACHE II score was significantly poorer in comparison with other patients. CONCLUSION: The serum uric acid level, which might be elevated by the various critical stimuli on admission, was an independent predictor in patients who were emergently hospitalized in the intensive care unit. The serum uric acid level is therefore useful as a surrogate biomarker for critical patients in the intensive care unit.

DOI： 10.1177/2048872618822473

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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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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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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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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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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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DOI： 10.1016/j.ijcard.2019.08.012

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

DOI： 10.2169/internalmedicine.2757-19

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

DOI： 10.1177/2048872617703061

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

DOI： 10.1002/ehf2.12414

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

DOI： 10.1002/ehf2.12390

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The aim of the present study was to elucidate trends in managing acute heart failure (AHF) patients who require intensive care over a 19-year period. We evaluated a total of 1,475 AHF patients, comparing patient backgrounds, in-hospital management, and prognosis according to the year of admission (2000s group, n = 608 and 2010s group, n = 867). A multivariate logistic regression analysis revealed that age (≥75 years; odds ratio [OR] 1.334, 95% confidence interval [CI] 1.048 to 1.700), systolic blood pressure (<100 mm Hg; OR 1.934, 95% CI 1.170 to 3.198), left ventricular ejection fraction (>40%; OR 1.441, 95% CI 1.125 to 1.847), and prognostic nutritional index (severe; OR 1.865, 95% CI 1.224 to 2.841) were independently associated with admission in the 2010s group. The use of intra-aortic balloon pumping and noninvasive positive pressure ventilation increased significantly, whereas the need for endotracheal intubation and administration of furosemide and carperitide in the 2010s group decreased significantly compared with the 2000s group. Tolvaptan therapy was introduced from 2010. The duration of intensive care unit admission and total hospitalization in the 2010s group (4 [3 to 6] and 23 [15 to 40] days, respectively) were significantly shorter than in the 2000s group (5 [4 to 8] and 30 [20 to 54] days, respectively). A Kaplan-Meier survival curve analysis showed the survival rate of the 2010s group was significantly poorer compared with the 2000s group (hazards ratio 1.435, 95% CI 1.113 to 1.851). After propensity score matching, the 365-day mortality rates of the 2 groups did not significantly differ. In conclusion, the condition of AHF patients became more critical year by year, leading to poorer long-term prognosis despite improved treatment strategy. These findings will be useful for managing AHF in the next pandemic era.

DOI： 10.1016/j.amjcard.2019.06.025

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PURPOSE: We sought to use non-contrast-enhanced T1 mapping to determine the native T1 values required to identify myocardial fibrosis in patients with dilated cardiomyopathy (DCM). METHODS: A total of 25 patients with DCM and 15 healthy controls were enrolled. All subjects underwent T1 mapping using modified look-locker inversion recovery, and the patients underwent late gadolinium-enhancement (LGE) imaging. Basal and mid-ventricular levels were divided into eight segments and the T1 value was measured in each segment. The T1 values of septal segments with LGE were compared with those of the septal segments without LGE, the minimum T1 value of each patient, and the T1 values of the normal septal myocardium. RESULTS: Late gadolinium-enhancement was present in 12 septal segments (24.0%) from 10 patients (40.0%). T1 values were significantly higher in septal segments with LGE than in those without (1373.7 vs. 1288.0 ms; P = 0.035) or in normal septal myocardium (1209.1 ms; P < 0.01). A receiver operating characteristic analysis revealed the appropriate cutoff value of 1349.4 ms for identifying LGE with a sensitivity of 75% and specificity of 92.1%. When the minimum T1 value + 1.2 standard deviation (SD) was used as the threshold, the sensitivity was 75% and specificity was 89.5%. CONCLUSION: Non-contrast-enhanced T1 mapping can be used for assessment of myocardial fibrosis associated with DCM by using the appropriate threshold.

DOI： 10.2463/mrms.mp.2017-0136

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Background: The relationship between the serum level of uric acid (UA) and the acute kidney injury on admission in patients with acute heart failure (AHF) remain unclear. Methods and results: A total of 1326 AHF patients were screened, and data for 1047 patients who were admitted to the intensive-care unit were analyzed. The patients were assigned to a low-UA group (UA ≤ 7.0 mg/dl, n = 569) or a high-UA group (UA > 7.0 mg/dl, n = 478) according to their UA level at admission. Acute kidney injury (AKI) at admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value: no-AKI (n = 736) or AKI (n = 311). The patients were therefore assigned to four groups: low-UA/no-AKI (n = 428), high-UA/no-AKI (n = 308), low-UA/AKI (n = 141) and high-UA/AKI (n = 170). The high-UA patients were significantly more frequent in the AKI group than in the non-AKI group among all patients and the non-chronic kidney injury (CKD) cohort. A Kaplan-Meier curve showed a significantly lower 365-day survival rate in the high-UA/AKI group than in the other groups. The multivariate Cox regression model identified only high-UA/AKI as an independent predictor of 365-day mortality (hazard ratio [HR]: 2.511, 95% confidence interval [CI] 1.671-3.772 in all AHF patients, HR: 1.884, 95% CI 1.022-3.473 in non-CKD patients and HR: 3.546, 95% CI 2.136-5.884 in CKD patients). Conclusion: An elevated serum UA level complicated with AKI was an independent predictor of mortality in patients with severely decompensated AHF.

DOI： 10.1016/j.ijcha.2019.03.005

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Patients diagnosed with acute coronary syndrome (ACS) during winter have worse outcomes; however, mechanisms driving this trend are unclear. We examined coronary culprit lesion morphologies using optical coherence tomography (OCT). Features and outcomes were retrospectively compared between patients admitted with ACS in winter (W-ACS; n = 390) and in other seasons (O-ACS; n = 1,027). Angiography and OCT results were analyzed in patients who underwent OCT examination (173 patients in W-ACS and 450 in O-ACS). On initial angiography, minimum lumen diameter was smaller (median; 0.12 mm vs 0.25 mm, p = 0.021) and Thrombolysis in myocardial infarction flow grade was worse (Thrombolysis in myocardial infarction 0/1; 57% vs 44%, p = 0.005) in W-ACS. OCT performed before coronary interventions or just after intracoronary thrombectomy showed that plaque rupture (56% vs 46%) and calcified nodules (8% vs 5%) were more prevalent, and plaque erosion (37% vs 49%) was less prevalent in W-ACS (p = 0.039 for all 3 variables). At 2-year follow-up for all admitted ACS patients, Kaplan-Meier estimates showed higher cardiac mortality in W-ACS (11.8% vs 8.3%, p = 0.043). Multivariate Cox proportional hazard analysis showed that patients in W-ACS group had a 1.5-fold increased risk of cardiac death within 2 years after adjusting for traditional cardiovascular risk factors (hazard ratio, 1.54 [95% confidence interval, 1.06 to 2.23]; p = 0.024). In conclusion, patients diagnosed with ACS during winter had worse angiographic results and OCT revealed less plaque erosion (more plaque rupture or calcified nodules) at the culprit lesions, which may be partly associated with worse cardiac mortality within 2 years.

DOI： 10.1016/j.amjcard.2019.03.045

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DOI： 10.1159/000496053

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A highly conductive textile was woven from nano-fibers coated with the PEDOT-PSS polymer. The aim of this study was to assess the usefulness of textile electrodes for ECG recording as a smart garment. Electrode textile pads and lead wires were sewn to the lining of sportswear and their tolerability to repeated washings were tested up to 150 times. The electrical conductivity of the textile electrode remained functional for up to 50 machine washes. To assess the level of motion artifacts or noise during the daily monitoring of ECG, a single lead ECG with conventional or textile electrodes was recorded during supine rest, seated rest, upright trunk rotation (i.e., twisting), and stepping movement in 66 healthy adults. A Holter system was used for data storage and analysis. ECG patterns of P, QRS, and T waves were comparable between the conventional and textile electrodes. However, the signal-to-artifact-and/or-noise ratio (SAR) during twisting was larger in the textile electrodes than in the conventional electrodes. No skin irritation was seen in the textile electrodes. The single lead textile electrodes embedded in an inner garment were usable for continuous and/or repeated ECG monitoring in daily life except during vigorous trunk movement.

DOI： 10.1007/s00380-019-01347-8

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

DOI： 10.1007/s13300-018-0480-7

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

DOI： 10.1002/ehf2.12264

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AIMS: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are increasingly frequent in Asia and commonly coexist in patients. However, the prevalence of COPD among Asian patients with HF and its impact on HF treatment are unclear. METHODS AND RESULTS: We compared clinical characteristics and treatment approaches between patients with or without a history of COPD, before and after 1:2 propensity matching (for age, sex, geographical region, income level, and ethnic group) in 5232 prospectively recruited patients with HF and reduced ejection fraction (HFrEF, <40%) from 11 Asian regions (Northeast Asia: South Korea, Japan, Taiwan, Hong Kong, and China; South Asia: India; Southeast Asia: Thailand, Malaysia, Philippines, Indonesia, and Singapore). Among the 5232 patients with HFrEF, a history of COPD was present in 8.3% (n = 434), with significant variation in geography (11.0% in Northeast Asia vs. 4.7% in South Asia), regional income level (9.7% in high income vs. 5.8% in low income), and ethnicity (17.0% in Filipinos vs. 5.2% in Indians) (all P < 0.05). Use of mineralocorticoid receptor antagonists and diuretics was similar between groups, while usage of all β-blockers was lower in the COPD group than in the non-COPD group in the overall (66.3% vs. 79.9%) and propensity-matched cohorts (66.3% vs. 81.7%) (all P < 0.05). A striking exception was the Japanese cohort in which β-blocker use was high in COPD and non-COPD patients (95.2% vs. 91.2%). CONCLUSIONS: The prevalence of COPD in HFrEF varied across Asia and was related to underuse of β-blockers, except in Japan.

DOI： 10.1002/ehf2.12228

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BACKGROUND: Little information is available on non-cardiovascular (CV) death in acute heart failure (AHF) patients. The present study determined the incidence, time course, and factors associated with long-term non-CV death in AHF patients in a real-world setting. METHODS: The ATTEND registry, a nationwide, prospective observational multicenter cohort study, included 4842 consecutive patients hospitalized for AHF. The primary endpoint of the present study was non-CV death. RESULTS: Median follow-up duration from admission was 513 (range, 385-778) days. Over the study period, 1183 patients died; 356 deaths (30.1%) were non-CV related. The proportion of non-CV deaths increased in the later follow-up phase (0-180days, 26.7%; 181-360days, 38.4%; >360days, 36.6%, p<0.001). After adjustment for all variables at baseline, age (hazard ratio [HR] 1.6 per decade, p<0.001) and non-cardiac comorbidities including chronic obstructive pulmonary disease (HR 1.58, p=0.003), history of stroke (HR 1.44, p=0.011), renal insufficiency (HR 1.07, per 10ml/min/1.73m2 decrease in estimated glomerular filtration, p=0.015), and hemoglobin (HR 1.15 per 1.0g/dl decrease, p<0.001) were strongly associated with non-CV death. Other predictors included ischemic etiology (HR 1.33, p=0.023), prior hospitalization for heart failure (HR 1.34, p=0.017), C-reactive protein (HR 1.04, p<0.001), and statin use (HR 0.70, p=0.016). CONCLUSIONS: The incidence of non-CV death was high in patients with AHF, accounting for 30% of long-term mortality. Furthermore, the proportion of non-CV death increased in the later follow-up phase. Better understanding of non-CV death and more comprehensive treatment of non-CV comorbidities are vital to further improving prognosis in AHF patients.

DOI： 10.1016/j.ijcard.2017.09.004

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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 < 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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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 < 200 mg/dl (decreased BG). The elevated and decreased BG patients were further divided into another three groups: 200 mg/ml ≤ BG < 300 mg/dl (mild-elevated), 300 mg/ml ≤ BG < 400 mg/dl (moderate-elevated) and BG ≥ 400 mg/ml (severe-elevated); and 150 mg/ml ≤ BG < 200 mg/dl (mild-decreased), 100 mg/ml ≤ BG < 150 mg/dl (moderate-decreased) and BG < 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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Authorship：Corresponding author   Language：English   Publisher：Springer Tokyo  

T1 mapping using cardiac magnetic resonance (CMR) is useful for myocardial assessment. However, its prognostic value is not well defined. The aim of this study was to determine whether T1 mapping with CMR can predict reverse cardiac remodeling in patients with non-ischemic dilated cardiomyopathy (NIDCM). We also investigated the predictive prognostic value of T1 mapping with CMR in these patients. We included 33 patients with NIDCM admitted to Nippon Medical School Hospital between February 2012 and October 2015. All patients underwent CMR and echocardiography for clinical assessment within 1 month of admission (13 ± 16 days). Follow-up echocardiography was performed no sooner than 6 months after the initial echocardiogram (536 ± 304 days). We evaluated the correlations between native and post-contrast T1 values/extracellular volume fraction (ECV) and the difference in left ventricular ejection fraction (ΔLVEF) determined at baseline and follow-up echocardiography. No correlation was noted between ΔLVEF and native (p = 0.150, r = - 0.256) or post-contrast T1 values (p = 0.956, r = - 0.010). However, a significant and substantial correlation was found between ΔLVEF and ECV (p = 0.043, r = - 0.355). Four patients were hospitalized for heart failure (HF), but no cardiovascular-related deaths occurred over a median follow-up period of 34 months (interquartile range 25-49 months). Kaplan-Meier curves stratified by the median value of ECV were created. The higher ECV groups experienced a significantly higher incidence of HF-related hospitalization (p = 0.0159). ECV measured by CMR can predict improvements in LVEF in patients with NIDCM. In addition, ECV may be a predictive factor for HF-related hospitalization.

DOI： 10.1007/s00380-018-1154-0

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Language：English   Publisher：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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After alcohol septal ablation (ASA), regression of left ventricular hypertrophy (LVH) has been observed in several studies using echocardiography or cardiac magnetic resonance, and favorable changes of myocardial excitation have been expected. However, no studies have focused on the alteration of electrocardiography (ECG) findings after ASA. Therefore, we evaluated serial changes in ECG parameters during the chronic phase after ASA for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). From 1998 to 2014, we performed 187 ASA procedures in 157 drug-refractory HOCM patients. After excluding patients who underwent dual-chamber pacing therapy and who underwent staged or repeat ASA within 2 years after the index ASA, 25 patients without bundle branch block and additional pacemaker implantation were enrolled in the main study group. ECGs, echocardiograms, and clinical follow-up data were evaluated at baseline and, 1, 6, 12, and 24 months after ASA. Patients with bundle branch block or additional pacemaker implantation were assigned in a referential group (n = 79), in which the echocardiographic changes between baseline and at 1 year were evaluated. Sokolow-Lyon index (SLi), Cornell index, and total 12-lead QRS amplitude significantly decreased during 2-year follow-up after ASA. SLi and Cornell index significantly decreased from 6 to 12 months (p < 0.05 vs. p < 0.01). Changes in SLi were significantly associated with changes in the interventricular septal thickness (r = 0.54, p < 0.005), left ventricular mass index (r = 0.40, p = 0.050), and peak creatine phosphokinase level (r = -0.41, p = 0.042), but not in the Cornell index and 12-lead QRS amplitude. In the comparison between baseline and at 1 year, significant improvements in the interventricular septal thickness, posterior wall thickness, left atrial size, E/A ratio, and E/e' were observed in the echocardiographic study. Changes of SLi reflected regression of LVH after ASA with the best correlation. During the chronic phase after ASA, LVH regression was confirmed by echocardiographic and ECG parameters.

DOI： 10.1007/s00380-017-1053-9

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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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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 < 35, n = 331), middle-PNI (35 ≤ PNI < 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 < 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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BACKGROUND: While preinfarction angina pectoris (pre-IA) is recognized as favorable effects on acute myocardial infarction (AMI), the detail has not been fully investigated. The aims of the current study were to clarify patient characteristics, lesion morphologies determined by optical coherence tomography (OCT), and cardiac outcomes related to pre-IA in patients with AMI. METHODS: Clinical data and outcomes were compared between AMI patients with pre-IA (pre-IA group, n = 507) and without pre-IA (non-pre-IA group, n = 653). Angiography and OCT findings were analyzed in patients with pre-intervention OCT and compared between groups of pre-IA (n = 219) and non-pre-IA (n = 269). RESULTS: ST-segment elevation myocardial infarction (61% vs. 75%, p < 0.001) and cardiogenic shock (8% vs. 14%, p = 0.001) were less prevalent in pre-IA group. Peak creatine kinase-MB levels were lower in pre-IA group (median 83 IU/mL vs. 126 IU/mL, p < 0.001). In pre-intervention coronary angiography findings, initial TIMI flow grade 0/1 (43% vs. 56%, p = 0.019) and Rentrop collateral circulation 0/1 (69% vs. 79%, p = 0.018) were less frequently observed in pre-IA than in non-pre-IA patients. In post-thrombectomy OCT images, plaque rupture (39% vs. 56%, p = 0.003) and red thrombi (42% vs. 54%, p = 0.027) were also less frequently observed in pre-IA group. Kaplan-Meier estimate survival curves showed that cardiac death at 12-months was lower in pre-IA group than in non-pre-IA group (6.9% vs. 10.1%, p = 0.036). CONCLUSIONS: Patients with pre-IA had less severe AMI on admission, smaller infarction size, and more favorable long-term survival, which may be caused by difference of lesion morphology between patients with and without pre-IA.

DOI： 10.1016/j.ijcard.2018.07.074

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

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

DOI： 10.1159/000477825

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

DOI： 10.1016/j.amjcard.2017.05.051

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DOI： 10.1016/j.jjcc.2017.02.001

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

DOI： 10.1177/2048872615593388

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本循環器学会  

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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 (≤1 atherosclerosis risk factor) and a high-risk group (≥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 < 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 ≥3, HR 0.209, 95 % CI 0.093-0.472, p < 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 < 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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BACKGROUND: The purposes of this study were to assess the usefulness of myocardial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for evaluating myocardial metabolic status in hypertrophic cardiomyopathy (HCM) and the therapeutic efficacy of alcohol septal ablation (ASA) in hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Thirty HCM patients (64.4±10.5 years, 14 male, 12 hypertrophic non-obstructive cardiomyopathy [HNCM], 16 HOCM, and 2 dilated phase of HCM) underwent 18F-FDG-PET/CT. 18F-FDG uptake was semi-quantitatively evaluated using an uptake score in each 17 segment and the entire LV or regional standardized uptake value (SUV). RESULTS: 18F-FDG uptake was observed mostly in a hypertrophied myocardium in HNCM patients, whereas 18F-FDG was extensively accumulated beyond the hypertrophied myocardium in HOCM patients. There was a positive correlation between the summed uptake score of 18F-FDG and high-sensitive troponin T level in HNCM patients (r = 0.603, p = 0.049), whereas the score was positively correlated with brain natriuretic peptide level (r = 0.614, p = 0.011) in HOCM patients. In 10 patients who received ASA, the maximum SUV of the entire LV was significantly reduced from 5.6±2.6 to 3.2±2.1 (p = 0.040) after ASA. Reduction of that maximum SUV was particularly significant in the lateral region (from 5.5±2.6 to 2.9 ±2.2, p = 0.024) but not significant in the anteroseptal region (from 4.5±2.6 to 2.9±1.6, p = 0.12). CONCLUSION: Extensive 18F-FDG uptake beyond the hypertrophied myocardium was observed in HOCM. ASA attenuates 18F-FDG uptake in a remote lateral myocardium.

DOI： 10.1371/journal.pone.0188479

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Three-dimensional (3D) cardiac magnetic resonance (MR) imaging has several advantages, including the easy coverage of the entire heart without misregistration, reduction of breath-holding times, and availability for postprocessing reconstruction. These advantages are associated with some techniques such as breath-hold or navigator gating and parallel imaging. However, the image quality of 3D cardiac MR images is compromised by the use of a shorter repetition time and parallel imaging. Thus, a steady-state free precession sequence, contrast agent administration, and presaturation pulses are used to maintain the image quality. In this review, we introduce the MR imaging techniques used in 3D cardiac MR imaging and demonstrate the typical 3D cardiac MR images, followed by discussion about their advantages and disadvantages.

DOI： 10.2463/mrms.rev.2016-0116

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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 AHF patients were enrolled in this study. The patients were assigned to four groups according to their BMI values: severely thin (n = 11, BMI <16), normal/underweight (n = 579, 16 ≤ BMI <25), overweight (n = 178, 25 ≤ BMI <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) <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 ≥140 mmHg and be relatively young, while severely thin patients tended to have SBP <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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We evaluated a cohort of patients treated with alcohol septal ablation (ASA) to identify predictive factors for repeat ASA. We compared 15 patients who underwent repeat ASA procedures (group R) with 69 patients not requiring repeat procedures (group S) in terms of clinical parameters and morphologic cardiac magnetic resonance. Group R showed higher number of hypertrophic segments (thickness ≥15 mm) in the basal left ventricular level (2.8 ± 1.7 vs 1.7 ± 0.8, p = 0.009) than group S. In the multivariate analysis, diuretics use (adjusted odds ratio 5.8, 95% confidential interval [CI] 1.04 to 32.2, p = 0.045) and the number of non-anteroseptal extended hypertrophy segments at the basal level were independent predictors of a repeat ASA procedure (adjusted odds ratio 3.64/segment, 95% CI 1.40 to 9.4, p = 0.008). One repeat ASA among 21 patients without non-anteroseptal hypertrophy and 1 repeat ASA among 29 patients without posteroseptal hypertrophy were observed; however, 7 of the 14 patients with ≥2 segments of non-anteroseptal hypertrophy received repeat ASA. In conclusion, cardiac magnetic resonance-based cross-sectional investigation elucidated non-anteroseptal hypertrophy (≥2 segments) to be a crucial predictor of repeat ASA. ASA is useful for patients with regional hypertrophy in the basal anteroseptal, but not posteroseptal region, and without heart failure requiring diuretics.

DOI： 10.1016/j.amjcard.2017.03.248

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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<0.001) with a significant interaction (p-value for interaction<0.001). The prognosis, including cardiovascular death, was significantly poorer among elderly female patients (≥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 (≥79 years) was associated with adverse outcomes in female patients with AHF.

DOI： 10.1016/j.jjcc.2016.11.015

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Language：Japanese   Publisher：日本心臓血管内視鏡学会  

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DOI： 10.1007/s00392-016-0981-1

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Autophagy is a process of bulk protein degradation and organelle turnover, and is a current therapeutic target in several diseases. The present study aimed to clarify the significance of myocardial autophagy of patients with dilated cardiomyopathy (DCM). Left ventricular endomyocardial biopsy was performed in 250 consecutive patients with DCM (54.9±13.9 years; male, 79%), initially presenting with decompensated heart failure (HF). The association of these findings with HF mortality or recurrence was examined. Myofilament changes, which are apparent in the degenerated cardiomyocytes of DCM, were recognized in 164 patients (66%), and autophagic vacuoles in cardiomyocytes were identified in or near the area of myofilament changes in 86 patients (34%). Morphometrically, fibrosis (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93 to 0.99) and mitochondrial abnormality (OR, 2.24; 95% CI, 1.23 to 4.08) were independently related with autophagic vacuoles. During the follow-up period of 4.9±3.9 y, 24 patients (10%) died, including 10 (4%) who died of HF, and 67 (27%) were readmitted for HF recurrence. Multivariate analysis identified a family history of DCM (hazard ratio [HR], 2.117; 95% CI, 1.199 to 3.738), hemoglobin level (HR, 0.845; 95% CI, 0.749 to 0.953), myofilament changes (HR, 13.525; 95% CI, 5.340 to 34.255), and autophagic vacuoles (HR, 0.214; 95% CI, 0.114 to 0.400) as independent predictors of death or readmission due to HF recurrence. In conclusion, autophagic vacuoles in cardiomyocytes are associated with a better HF prognosis in patients with DCM, suggesting autophagy may play a role in the prevention of myocardial degeneration.

DOI： 10.1080/15548627.2016.1145326

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DOI： 10.1016/j.mri.2016.05.008

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Background: COPD is concomitantly present in similar to 30% of patients with heart failure. Here, we investigated the pulmonary function test parameters for left ventricular (LV) diastolic dysfunction and the relationship between pulmonary function and LV diastolic function in patients with COPD.
Patients and methods: Overall, 822 patients who underwent a pulmonary function test and echocardiography simultaneously between January 2011 and December 2012 were evaluated. Finally, 115 patients with COPD and 115 age-and sex-matched control patients with an LV ejection fraction of &gt;= 50% were enrolled.
Results: The mean age of the patients was 74.4 +/- 10.4 years, and 72.3% were men. No significant differences were found between the two groups regarding comorbidities, such as hypertension, diabetes mellitus, and anemia. The index of LV diastolic function (E/e') and the proportion of patients with high E/e' (defined as E/e' &gt;= 15) were significantly higher in patients with COPD than in control patients (10.5% vs 9.1%, P=0.009; 11.3% vs 4.3%, P= 0.046). E/e' was significantly correlated with the residual volume/total lung capacity ratio. Univariate and multivariate analyses revealed severe COPD (Global Initiative for Chronic Obstructive Lung Disease III or IV) to be a significant predictive factor for high E/e' (odds ratio [OR] 5.81, 95% confidence interval [CI] 2.13-15.89, P= 0.001 and OR 6.00, 95% CI 2.08-17.35, P= 0.001, respectively).
Conclusion: Our data suggest that LV diastolic dysfunction as a complication of COPD may be associated with mechanical exclusion of the heart by pulmonary overinflation.

DOI： 10.2147/COPD.S101082

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Language：English   Publisher：Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai)  

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 HF (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≤7.0mg/dl, n=495) or a high UA group (UA>7.0mg/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%CI: 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.

DOI： 10.1016/j.jjcc.2016.04.013

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DOI： 10.1371/journal.pone.0167645

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DOI： 10.1186/s12872-016-0340-1

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DOI： 10.1177/0284185115580840

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The hepatocyte nuclear factor 1β gene (HNF1B) is responsible for maturity-onset diabetes of the young type 5 (MODY5), which is characterized by early-onset diabetes mellitus and urogenital malformations. HNF1B is expressed during visceral endoderm formation. We identified a disruption of the great pancreatic artery in a patient with MODY5 with no pancreatic body or tail. Our finding supports the significance of HNF1B in the development of the pancreas.

DOI： 10.1038/hgv.2016.22

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DOI： 10.1016/j.ejim.2015.08.015

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Tagging CMR has been established as the standard reference for measurement of myocardial strain. The current 2D tagging technique requires multiple breath-holds to cover the whole heart and cannot show the 3D motions of the left ventricle. We performed fast 3-breath-hold 3D tagging with localized tagging preparation and complementary spatial modulation of magnetization in 10 patients with hypertrophic myocardial diseases and 6 normal volunteers. The left wall motion was observed at any view angle, which allowed for the identification of regional and global hypokinesis using the fast 3D tagging. Although a decrease in the circumferential strain and LGE were observed at the basal septum in hypertrophic cardiomyopathy, they were not located together in each patient. In hypertensive heart disease, the decrease in circumferential strain was observed more widely than LGE, and the summed strain of all segments was significantly decreased. The decrease in strain and LGE were observed diffusely in cardiac amyloidosis. In conclusion, fast 3-breath-hold 3D tagging is feasible for the regional and global strain analysis. The location of reduced circumferential strain is not necessarily the same as that of LGE and is related to the global cardiac function in patients with hypertrophic myocardial diseases.

DOI： 10.1155/2016/3749489

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Language：Japanese   Publisher：日本医科大学医学会  

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DOI： 10.1016/j.amjcard.2015.07.004

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DOI： 10.1016/j.amjcard.2015.07.004

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We retrospectively evaluated factors affecting the lifespan of schizophrenic patients, who are known to have a shorter life expectancy than healthy people, focusing on the relationship with QT prolongation associated with antipsychotics. In a total of 406 patients who died at Asai Hospital the mean age at death was compared between schizophrenic patients and nonpsychiatric patients. In deceased schizophrenic patients, drug-related factors, hematology results, and electrocardiographic findings for 3 years before death were compared with those for the same period in age-matched surviving schizophrenic patients. In addition, QT values in schizophrenic patients and healthy controls were evaluated by age group. The mean age at death was significantly younger in schizophrenic patients (63.4 +/- 2.63 years) than in nonpsychiatric patients (84.0 +/- 0.57 years) (p<0.001). Bivariate analysis between deceased and surviving schizophrenic patients showed significant differences in QT values at 2 years, 1 year, and 0.5 years before death and in AST and ALT values at 0.5.years before death. The incidence of QT prolongation in deceased schizophrenic patients (52.0%) was about twice as high as that in surviving schizophrenic patients (24.5%). Multiple logistic regression analysis suggested that the proportion of deceased patients was higher when QT intervals were longer and ALT values were relatively higher, even if within the normal range. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age (R2 = 0.9061 and 0.9276, respectively), and QT intervals in schizophrenic patients were significantly longer in the 30- to 70-year age groups. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age, and QT intervals in schizophrenic patients were significantly longer than those in medical checkup examinees in the same age groups. Deceased schizophrenic patients showed significantly longer QT intervals from 2 years before death than age-matched surviving schizophrenic patients. QT prolongation may influence the lifespan of schizophrenic patients, which are shorter than those of nonpsychiatric patients. This highlights the importance of following electrocardiographic findings and hematology results of schizophrenic patients over time.

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Language：English   Publisher：Springer Tokyo  

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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DOI： 10.1007/s00392-014-0774-3

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Dove Medical Press Ltd.  

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is present in approximately one-third of all congestive heart failure (CHF) patients, and is a key cause of underprescription and underdosing of β-blockers, largely owing to concerns about precipitating respiratory deterioration. For these reasons, the aim of this study was to evaluate the impact of β-blockers on the long-term outcomes in CHF patients with COPD. In addition, we compared the effects of two different β-blockers, carvedilol and bisoprolol. METHODS: The study was a retrospective, non-randomized, single center trial. Acute decompensated HF patients with COPD were classified according to the oral drug used at discharge into β-blocker (n=86; carvedilol [n=52] or bisoprolol [n=34]) and non-β-blocker groups (n=46). The primary endpoint was all-cause mortality between the β-blocker and non-β-blocker groups during a mean clinical follow-up of 33.9 months. The secondary endpoints were the differences in all-cause mortality and the hospitalization rates for CHF and/or COPD exacerbation between patients receiving carvedilol and bisoprolol. RESULTS: The mortality rate was higher in patients without β-blockers compared with those taking β-blockers (log-rank P=0.039), and univariate analyses revealed that the use of β-blockers was the only factor significantly correlated with the mortality rate (hazard ratio: 0.41; 95% confidence interval: 0.17-0.99; P=0.047). Moreover, the rate of CHF and/or COPD exacerbation was higher in patients treated with carvedilol compared with bisoprolol (log-rank P=0.033). In the multivariate analysis, only a past history of COPD exacerbation significantly increased the risk of re-hospitalization due to CHF and/or COPD exacerbation (adjusted hazard ratio: 3.11; 95% confidence interval: 1.47-6.61; P=0.003). CONCLUSION: These findings support the recommendations to use β-blockers in HF patients with COPD. Importantly, bisoprolol reduced the incidence of CHF and/or COPD exacerbation compared with carvedilol.

DOI： 10.2147/COPD.S79942

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DOI： 10.1016/j.amjcard.2015.05.006

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DOI： 10.1016/j.amjcard.2015.06.023

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DOI： 10.1093/eurheartj/ehu404

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Language：English   Publisher：Japanese Circulation Society  

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 (≥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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DOI： 10.1007/s10557-014-6565-2

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Language：English   Publisher：Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai)  

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 HF events (death, readmission-HF), 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.

DOI： 10.1016/j.jjcc.2014.03.002

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

DOI： 10.1111/jth.12608

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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 (7.5mg) 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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DOI： 10.1002/cbf.2973

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DOI： 10.1136/bmjopen-2014-005968

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DOI： 10.1016/j.cardfail.2014.07.278

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DOI： 10.1007/s00392-014-0717-z

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DOI： 10.1007/s00392-014-0748-5

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DOI： 10.1161/CIRCULATIONAHA.112.000602

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DOI： 10.1016/j.ijcard.2012.09.046

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

DOI： 10.1016/j.amjcard.2013.02.018

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DOI： 10.1016/j.ijcard.2013.07.032

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BACKGROUND: Central blood pressure (CBP) is superior to brachial blood pressure as a predictor of cardiovascular risk in patients with hypertension. There is currently no consensus regarding whether a direct renin inhibitor (DRI) selectively acts on CBP. METHODS: Thirty subjects with essential hypertension who showed a CBP of 140 mm Hg or higher after 12 weeks of treatment with a standard dose of a DRI (150 mg) were analyzed. The patients were randomly divided into 2 groups: the high-dose DRI group (n=15) received 300 mg of DRI per day, and the combination group (n=15) received both the standard dose of the DRI and a diuretic (12.5 mg of hydrochlorothiazide). The systolic blood pressure (SBP), CBP, and the augmentation index (AI) were determined before treatment and after 12 and 24 weeks of treatment. RESULTS: The SBP, CBP and AI were significantly decreased after 12 weeks of treatment with standard dose of the DRI (p<0.05). From 12 to 24 weeks after assignment the SBP and CBP were also significantly decreased in both the high-dose DRI group and the combination group. The high-dose DRI group showed a greater decrease in the CBP, but not in the SBP, than did the combination group (p<0.05). The AI decreased significantly from 12 to 24 weeks in the high-dose DRI group (p<0.05) but not in the combination group (p=0.14). CONCLUSIONS: Treatment with a DRI contributes to a decrease in the CBP and AI, and high-dose DRI therapy leads to a further decrease in the CBP and AI.

DOI： 10.1272/jnms.80.25

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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 <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 <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 ≥ 2. Kaplan-Meier survival analysis showed that any-cause death was significantly higher in patients with PCPS survival score ≤ 1 than in those with a score ≥ 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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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±38.9mmHg; CS 1, 80.9%; HR, 116.9±28.0beats/min) than in group D (SBP, 154.2±37.1mmHg; CS 1, 66.2%; HR, 108.6±31.4beats/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 ≥164mmHg [odds ratio (OR): 2.043; 95% confidence interval (CI): 1.383-3.109], HR ≥114beats/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.

DOI： 10.1016/j.jjcc.2012.10.004

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BACKGROUND: Cardiac magnetic resonance (CMR) imaging is an established method of detecting myocardial fibrosis related to prognosis in patients with dilated cardiomyopathy (DCM). Recent studies have found that (99m)Tc-methoxy-isobutyl-isonitrile (MIBI) and (123)I-15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) dual single-photon-emission computerized tomography (MIBI-BMIPP dual SPECT) can detect perfusion-metabolism mismatches. We compared MIBI-BMIPP dual SPECT with CMR findings and assessed their prognostic abilities to determine the significance of abnormal metabolism in patients with DCM. METHODS AND RESULTS: Fifty inpatients with DCM (age 58 ± 12 y; 14 female) were assessed with the use of MIBI-BMIPP dual SPECT and CMR. Perfusion-metabolism mismatches were identified mainly at the left ventricular free wall, whereas late gadolinium enhancement (LGE) was evident mostly at the septal wall. During a median follow-up of 33 months, 9 patients developed cardiac events including death, heart failure, and fatal arrhythmia. Event-free survival rates were significantly lower for patients with LGE plus a mismatch than with other abnormalities (P = .001). Among clinical and imaging variables, LGE plus a mismatch was significantly associated with cardiac events (hazard ratio 7.9, 95% confidence interval 1.8-35.6; P = .007). CONCLUSIONS: Coexisting LGE and a perfusion-metabolism mismatch accurately predict future cardiac events in patients with DCM.

DOI： 10.1016/j.cardfail.2013.05.009

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Hyponatremia is known to be a poor prognostic factor in patients hospitalized with heart failure (HF), however not well studied in Japan. The aims of this study were to characterize hyponatremic hospitalized patients with HF and to clarify the relations between hyponatremia and detailed in-hospital outcomes in Japan. Among 4,837 hospitalized patients with HF enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, patient characteristics and in-hospital mortality in those with hyponatremia were examined. Hyponatremia (sodium <135 mEq/L) was observed in 11.6% of patients. Patients with hyponatremia were of similar age, included fewer men, and had a higher proportion of previous hospitalizations for HF compared to those with normonatremia. On admission, lower heart rates and blood pressures and higher brain natriuretic peptide levels were observed in patients with hyponatremia. During hospitalization, inotrope levels and mechanical device use were significantly higher in patients with hyponatremia. Rates of all-cause and cardiac death were significantly higher in patients with hyponatremia, 15.0% and 11.4%, respectively, compared to 5.3% and 3.6%, respectively, in those with normonatremia. In hyponatremic hospitalized patients with HF, cardiac death accounted for 76.2% of all-cause death. In conclusion, the present study demonstrates that in Japan hyponatremia in patients hospitalized with HF is relatively common and is associated with a very high in-hospital mortality.

DOI： 10.1016/j.amjcard.2012.12.019

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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.

DOI： 10.1253/circj.CJ-12-0994

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The aim of the present study was to investigate whether percutaneous coronary intervention-related periprocedural myocardial infarction (MI) can be suppressed more significantly with high- compared with low-dose rosuvastatin. A total of 232 patients scheduled to undergo elective percutaneous coronary intervention within 5 to 7 days were assigned to groups that would receive either 2.5 or 20 mg/day of rosuvastatin (n = 116 each). The incidence of periprocedural MI did not significantly differ between the high and low-dose groups (8.7% vs 18.7%, p = 0.052). In patients who were not taking statins at the time of enrollment, high-dose rosuvastatin significantly suppressed periprocedural MI compared with the low dose (10.5% vs 30.0%, p = 0.037). The difference was not significant in patients who were already taking statins (high vs low dose 7.6% vs 10.6%, p = 0.582). In conclusion, the incidence of percutaneous coronary intervention-related periprocedural MI was reduced more effectively by high-dose than by low-dose rosuvastatin in statin-naive patients. However, low-dose rosuvastatin is sufficient for patients who are already taking statins. © 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2013.02.018

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BACKGROUND: Hospitalized heart failure (HHF) is a critical issue in Japan. To improve its management and outcomes, the clinical features, in-hospital management, and outcomes should be analyzed to improve the guidelines for HHF. METHODS AND RESULTS: The acute decompensated heart failure syndromes (ATTEND) registry is the largest study of HHF in Japan. The present report covers the clinical features and in-hospital management of HHF patients. The data from 4,842 enrolled patients have demonstrated that most Japanese HHF patients are elderly, with new onset, and a history of hypertension and orthopnea on admission. During hospitalization, furosemide and carperitide were commonly used and the length of stay was extremely long (mean 30 days), with 6.4% in-hospital mortality. CONCLUSIONS: The findings of the present study suggest the following: (1) the focus for hypertensive elderly and diabetic patients should be on primary prevention of HHF,(2) more intensive management with noninvasive positive pressure ventilation should be performed at the urgent stage, (3) it is necessary to clarify the clinical benefit of carperitide and angiotensin-receptor blockers, because they are commonly used in Japan, and (4) it is necessary to clarify the relationship between in-hospital mortality and length of stay from the viewpoint of both outcome and cost of patient care.

DOI： 10.1253/circj.CJ-13-0187

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DOI： 10.1161/CIRCULATIONAHA.112.000602

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BACKGROUND: Obesity is associated with an increased risk of heart failure (HF) but the relationship between changes in cardiac function and the specific pathological features of dilated cardiomyopathy (DCM) with obesity, remains unknown. METHODS: Endomyocardial biopsies from the left ventricle (LV) were obtained from 50 patients with DCM, at the first-onset of decompensated HF. Thirty patients were obese (obese-group: body mass index >30 kg/m(2)) and 20 were non-obese (lean-group). Clinical data were acquired at the admission, after one month and one year. RESULTS: The obese-group had higher systolic blood pressure (142.8 ± 33.9 vs 113.6 ± 18.7 mm Hg; p<0.001) and serum troponin-T level (0.049 ± 0.07 vs 0.020 ± 0.03 ng/mL; p=0.022) than the lean-group. LV ejection fraction (LVEF) was not significantly different between groups, but after one year the obese-group had an improved LVEF (57.0 ± 11.4 vs 44.3 ± 17.1; p=0.003). Light microscopy revealed that the obese-group had larger cardiomyocytes (17.2 ± 1.7 vs 16.4 ± 1.4 μm; p=0.033) and less myofilament lysis (37 vs 75%; p=0.008) with a higher density of lipid droplets (1.93 ± 0.8 vs 0.94 ± 0.7 /μm(2); p<0.001). Multivariate regression analysis revealed that independent predictors of LVEF improvement after 12 months were diuretics use, nuclear diameter, and absence of myofilament lysis (p=0.024, 0.012 and 0.028, respectively). CONCLUSIONS: Cardiac function in most patients with DCM with obesity is reversible and myocardial structural changes are trivial even at the ultrastructural level.

DOI： 10.1016/j.ijcard.2012.09.046

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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 HF within 1 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 < 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 AKI, 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.

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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 (10-20mg/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±318.6ng/ml) and control group (1292.7±384.7ng/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±235.1ng/ml) compared to control group (272.6±270.6ng/ml; p=0.001). HF events which were defined as death from HF, readmission to hospital for HF, 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.

DOI： 10.1016/j.jjcc.2012.01.009

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DOI： 10.1016/j.cardfail.2012.08.038

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

DOI： 10.1536/ihj.53.261

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

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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>7.45), normal group (n=178, 7.35≤ pH≤ 7.45), and acidosis group (n=344, pH<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.

DOI： 10.1016/j.jjcc.2012.06.004

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Disruption of vulnerable plaque and following thrombus formation are considered the main cause of acute coronary syndrome (ACS). Intracoronary angioscopy is an endoscopic technology that allows direct visualization of the coronary artery lumen and provides detailed information regarding plaque morphology in patients with coronary artery disease. The color and morphology of coronary plaque under angioscopy observation are proposed to be determinants for plaque stability. Angioscopically yellow plaque represents a thin-cap fibroatheroma, and is associated with a higher incidence of disruption and thrombus formation, and may be associated with future acute coronary syndromes. To circumvent the subjectivity of color interpretation, various quantitative methods have been proposed for identifying vulnerable plaques. Superior to other coronary imaging techniques such as VH IVUS and optical coherence tomography, angioscopy has impressively high sensitivity and specificity in detection of intraluminal thrombus. Angioscopy can also be used as an adjunctive technique during catheter intervention by directly visualizing the thrombus, stent struts and proliferating neointima. The time course and pattern of neointima coverage, as seen by angioscopy, various among different stent systems. Angioscopic assessment of serial changes after stent implantation may have potential benefits on patient's management after coronary stenting.

DOI： 10.1007/s12928-011-0055-2

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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 (B-S; Respironics, Merrysville, PA, USA) period (2005-2007, n = 176) or BiPAP-Vision (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 < 0.05; 7.05 ± 0.08 vs. 7.27 ± 0.14, B-V period, p < 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.

DOI： 10.1016/j.jjcc.2010.10.004

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OBJECTIVES: Peripheral blood mononuclear cells (PBMCs) increase after acute myocardial infarction (AMI) and infiltrate to the infarct region. However, its impact on left ventricular (LV) remodeling remains unclear. The purpose of the present study was to clarify whether elevated PBMC count contributed to LV remodeling in patients with AMI. SUBJECTS AND METHODS: A total of 131 patients with AMI were recruited. White blood cell (WBC), monocyte, and lymphocyte counts were measured at presentation and every 24h for five days after presentation. The correlation between PBMC count and LV remodeling was evaluated. LV remodeling was defined as an increase of LV end-diastolic volume index ≥ 10% at the 6-month follow-up left ventriculography. RESULTS: Forty-eight patients had LV remodeling. Peak WBC (p=0.008), peak monocyte (p=0.001), and peak PBMC (p<0.001) counts were significantly greater in patients with LV remodeling than those without remodeling. Multivariate analysis revealed the peak PBMC count ≥ 3600/mm(3) was an independent predictor of LV remodeling [relative risk (RR) 3.243, p=0.011]. CONCLUSION: Increased PBMC count is significantly correlated with LV remodeling, thus suggesting that PBMCs play a pivotal role for the development of LV remodeling after AMI.

DOI： 10.1016/j.jjcc.2010.10.003

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

DOI： 10.4020/jhrs.27.OP49_3

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DOI： 10.1016/j.ijcard.2011.09.020

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

DOI： 10.1016/j.ijcard.2008.11.154

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

DOI： 10.1016/j.ahj.2010.03.019

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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 μg/kg, and the continuous injection of 60-100 μg/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 >140 mm Hg, n=10) and low SBP group (baseline SBP <140 mmHg, 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.

DOI： 10.1016/j.jjcc.2010.07.007

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

DOI： 10.1536/ihj.51.383

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Language：English   Publisher：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 < 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 ΔMMPs, defined as the changes in MMPs from day 1 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 day 1 and day 3. The results of the multivariate logistic regression model for predicting HF events found that the specific factor for HF events was ΔMMP-2. Cutoff values of ΔMMP-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 ΔMMP-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 AHF.

DOI： 10.1536/ihj.51.404

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

DOI： 10.1536/ihj.51.383

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Language：English   Publisher：NATURE PUBLISHING GROUP  

Continuous positive airway pressure (CPAP) treatment improves endothelial function and sympathetic activity in patients with obstructive sleep apnea (OSA). However, the long-term effects of CPAP on pulse wave velocity (PWV), which reflects arterial stiffness that is associated with cardiovascular events, have not been evaluated in OSA patients with or without hypertension (HT). In this study, 212 male OSA patients who had been receiving CPAP treatment for 2 years and were divided into two groups, those with HT (n=114) and those without (n=98), were studied. In both HT and normotensive (NT) patients, PWV decreased significantly over the first 6 months of treatment (P=0.005 and 0.010, respectively), before increasing gradually from 6 to 24 months. Body mass index (BMI), body weight, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels decreased significantly in the HT group over the 2 years of CPAP treatment (P<0.001 for all). In contrast, only HR decreased significantly in the NT group over the 2 years of treatment (P<0.001). Multivariate regression analysis revealed that age (P=0.008), decreases in DBP (P<0.001) and HR (P<0.001) and higher initial levels of serum high-density lipoprotein-cholesterol (P=0.040) were independent factors related to changes in PWV over the 2 years of CPAP treatment in all patients. In conclusion, we found a significant decrease in PWV in both NT and HT patients after 6 months of CPAP treatment. In HT patients, long-term CPAP treatment significantly decreases blood pressure, which may contribute to explain the PWV improvement.

DOI： 10.1038/hr.2010.77

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BACKGROUND: It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. METHODS AND RESULTS: The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 +/-9 vs 21 +/-2 mmHg in the control (n=6); P<0.01). Systolic RVP was also less in the arotinolol group (41 +/-3 vs 91 +/-14 mmHg in the control, P<0.05) without differences in BP. It also significantly reduced the RV/body weight ratio (0.58 +/-0.01 vs 0.77 +/-0.04 mg/g; P<0.01). Furthermore, the myocyte width was significantly decreased in the arotinolol group. CONCLUSIONS: The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH.

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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 stent 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 1 case. Subsequent cardiac tamponade occurred in 3 patients who required pericardiocentesis, and 1 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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BACKGROUND: Experimental study has shown that blunted arterial baroreflex function markedly attenuated inotropic responses to a phosphodiesterase inhibitor (PDEI) even in normal hearts. However, whether arterial baroreflex function is related to the inotropic responsiveness to a PDEI has not been clarified in human heart failure (HF). HYPOTHESIS: The goal of this study was to examine the relationship between inotropic responses to a PDEI and arterial baroreflex sensitivity in human HF. METHODS: Twelve patients with HF were examined, and hemodynamic responses to milrinone (12.5, 25, and 50 microg/kg, intravenous injection) and arterial baroreflex sensitivity were assessed by pulse interval-left ventricular (LV) systolic pressure slope using nitroglycerin and phenylephrine. RESULTS: Milrinone (25 microg/kg) significantly increased LV dP/dt. Arterial baroreflex sensitivity was only one predictor of inotropic responses to milrinone by multivariate analysis; a strong positive correlation was also found between LV dP/dt and baroreflex sensitivity (y = 6.656X - 3.326, r = 0.93, p = 0.000). CONCLUSION: Inotropic effects of milrinone, a PDEI, correlated significantly with arterial baroreflex sensitivity, suggesting that the more baroreflex function was impaired, the more the inotropic effect of a PDEI was depressed in human HF.

DOI： 10.1002/clc.4960290608

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

DOI： 10.1152/ajpheart.01034.2002

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

DOI： 10.1161/01.HYP.0000073843.56046.45

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

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DOI： 10.1006/jmcc.2001.1413

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.cir.103.19.2382

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.atv.20.6.1493

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DOI： 10.1161/01.res.86.7.802

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/01.cir.100.20.2113

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：American Society for Clinical Investigation  

DOI： 10.1172/jci7418

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DOI： 10.1016/s0002-9149(99)00266-0

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

DOI： 10.1152/ajpheart.1999.276.5.h1699

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DOI： 10.1161/01.res.84.6.735

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DOI： 10.1172/jci4848

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

DOI： 10.1152/ajpheart.1998.275.6.h2219

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DOI： 10.1161/01.cir.98.13.1342

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：American Society for Clinical Investigation  

DOI： 10.1172/jci1530

CiNii Books

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DOI： 10.1161/01.res.82.4.416

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

DOI： 10.1152/ajpcell.1997.273.6.c1957

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DOI： 10.1006/jmcc.1997.0377

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DOI： 10.1161/01.cir.95.8.2130

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Traditional inotropic agents, e.g., those that increase myocardial contraction through enhanced cyclic AMP or those that increase contractility at a relatively high O2 cost are frequently not useful in the clinical setting. Accordingly, newer agents that operate through different mechanisms have been synthesized. The goal of the present study was to compare the effects of a new Ca2+ promotor, BAY y 5959, with more traditional inotropic agents, dobutamine and milrinone, in 11 conscious dogs chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV internal diameter, wall thickness, coronary blood flow, and arterial and coronary sinus O2 content. Equi-inotropic doses of BAY y 5959 (20 microg x kg(-1) x min(-1)), dobutamine (10 microg x kg(-1) x min(-1)), and milrinone (10 microg x kg(-1) x min(-1)) were selected, which increased the LV rate of pressure development in sinus rhythm by 71-78% from similar baselines. Heart rate rose with dobutamine (+24 +/- 4%) and milrinone (+23 +/- 2%) but fell with BAY y 5959 (-35 +/- 3%). Dobutamine increased myocardial O2 consumption (MV(O2)) by 88 +/- 10%. In contrast, MV(O2) increased less with BAY y 5959 (+9 +/- 3%) and milrinone (+16 +/- 5%; P &lt; 0.05). Furthermore, mechanical efficiency was also calculated either with direct measurement of cardiac output or by pressure-volume loops. Dobutamine and milrinone did not change efficiency; however, BAY y 5959 increased efficiency by 19 +/- 5%. With the heart rate held constant, BAY y 5959 increased MV(O2) by 32 +/- 4% but still increased efficiency by 28 +/- 7%. Thus the Ca2+ promotor BAY y 5959 has unique features that might be desirable for clinical applications where inotropic support is indicated, but increased MV(O2) without enhanced mechanical efficiency is deleterious.

DOI： 10.1152/ajpheart.1997.272.2.h753

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

DOI： 10.1152/ajpheart.1997.272.1.h585

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Language：Japanese   Publisher：The Medical Association of Nippon Medical School  

DOI： 10.1272/jnms1923.58.597

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Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.22.31

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AIMS: This study aims to determine the implications associated with long-term prognosis of heart failure (HF) in patients with dilated cardiomyopathy (DCM) presenting initially as decompensated HF. We stratified the phase of DCM patients without late gadolinium enhancement (LGE) based on ultrastructural changes in cardiomyocytes. METHODS AND RESULTS: Left ventricular (LV) endomyocardial biopsy was performed in 55 consecutive DCM patients with initial decompensated HF. Ultrastructural changes in cardiomyocytes detected by electron microscopy were compared with data including LGE with cardiac magnetic resonance and HF recurrence. Of the 55 DCM patients, 24 (44%) showed LGE, and 26 (47%) showed recurrence decompensated HF, while 23 patients (42%) showed autophagic vacuoles in cardiomyocytes by electron microscopy. Multivariate analysis identified atrial fibrillation [hazard ratio (HR), 3.40; 95% confidence interval (CI), 1.45-7.98], haemoglobin level (HR, 0.82; 95% CI, 0.68-0.99), beta-blocker use (HR, 0.18; 95% CI, 0.05-0.74), and autophagic vacuoles (HR, 0.25; 95% CI, 0.09-0.65) as predictors of HF recurrence in the total patient population. In patients without LGE, only autophagic vacuoles were independent predictors of readmission because of HF (HR, 0.29; 95% CI, 0.09-0.90). In patients with LGE, atrial fibrillation (HR, 19.10; 95% CI, 2.97-123.09), and mid-linear LGE (HR, 12.96; 95% CI, 2.02-82.94) were independent predictors of readmission because of HF. CONCLUSIONS: In DCM patients with LGE, characterised by progression of LV remodelling, the LGE pattern was a predictor of HF recurrence, whereas in patients without LGE, absence of autophagic vacuoles was a predictor of HF recurrence.

DOI： 10.1002/ehf2.12662

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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