BACKGROUND & AIMS: :Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

背景与目标： ：代谢综合征（MetS）是心脏代谢危险因素的综合，包括肥胖，血脂异常，高血压和胰岛素抵抗，以及一系列继发性后遗症，例如非酒精性脂肪肝和舒张性心力衰竭。该综合征已被确定为21世纪全球最大的健康挑战之一。本文中，我们检查了饮食和盐皮质激素诱导的MetS的猪模型是否与人类研究中观察到的心血管，代谢，肠道菌群和功能性分类学表型密切相似。饲喂高脂，高盐和高糖饮食（超过12周）的患有乙酸脱氧皮质酮的高血压的长尾猪，进行高脂血症，高胰岛素血症，免疫组织学，超声心动图和血流动力学参数评估，并通过16S rRNA评估微生物组表型和功能元分类学和代谢组学分析。所有MetS动物均出现肥胖，高脂血症，胰岛素抵抗，高血压，脂肪肝，包括左心室肥大和左心房扩大在内的结构性心血管变化，以及循环饱和脂肪酸水平升高，所有这些均与人的表型保持一致。在该模型中，还观察到了门，属和属水平的α多样性和特定微生物群变化的减少。具体而言，该MetS的猪模型显示出增加的促炎细菌数量，以及循环肿瘤坏死因子-α的增加和继发性胆汁酸产生细菌的增加，这实质上影响了成纤维细胞生长因子-19的表达。最后，还注意到肠道保护细菌的显着减少和短链脂肪酸产生细菌的减少。总之，这些数据表明，饮食和盐皮质激素介导的猪代谢综合征生化和心血管柱头的发育导致人类肠道代谢疾病中模仿肠道关键微生物种群特征的暂时性肠道微生物组变化。代谢综合征包括全身性炎症，脂肪肝和胰岛素敏感性。猪心脏代谢疾病演变过程中的肠道微生物组变化概括了人类受试者中肠道菌群的变化，这些变化与促炎性细菌，胆汁酸和脂肪酸途径有关。此临床规模模型可能有助于将来进行干预性试验的设计，以在系统和器官水平上测试肠道营养不良与心脏代谢综合征之间的因果关系。

BACKGROUND & AIMS: BACKGROUND:Circulating cardiac troponin levels (cTn), representative of myocardial injury, are commonly elevated in heart failure (HF) and related to adverse clinical events. However, whether cTn represents a spectrum of risk in HF is unclear. METHODS:Baseline, 48-72-hour, and 30-day plasma cTnI was measured with the use of a new highly sensitive assay in 900 subjects with acute decompensated HF (ADHF) in ASCEND-HF. Multivariable models determined the relationship between cTnI and outcomes. RESULTS:The median (interquartile range) cTnI was 16.4 (9.3-31.6) ng/L at baseline, 14.1 (7.8-29.7) ng/L at 48-72 hours, and 11.6 (6.8-22.5) ng/L at 30 days. After additional adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP) to established risk predictors, both baseline (odds ratio [OR] 1.25; P = .03) and 48-72-hour (OR 1.43; P = .001) cTnI were associated with higher risk for death or worsening HF before discharge. However, only cTnI at 30 days was associated with 180-day death (hazard ratio 1.25; P = .007). There were no curvilinear associations between changing cTnI and clinical outcomes. CONCLUSIONS:Circulating cTnI level was associated with clinical outcomes in ADHF, but these observations diminished with additional adjustment for NT-proBNP. Although they likely represent a spectrum of risk in ADHF, these findings question the implications of changing cTnI levels during treatment.

背景与目标： 背景：代表心肌损伤的循环心肌肌钙蛋白水平（cTn）通常在心力衰竭（HF）中升高，并与不良临床事件相关。但是，尚不清楚cTn是否代表HF的风险范围。
方法：采用新的高灵敏测定法，对900例急性失代偿性HF（ADHF）的ASCEND-HF患者进行基线，48-72小时和30天血浆cTnI的测量。多变量模型确定了cTnI与结果之间的关系。
结果：基线时的cTnI中位数（四分位数范围）为16.4（9.3-31.6）ng / L，在48-72小时时为14.1（7.8-29.7）ng / L，在30天时为11.6（6.8-22.5）ng / L 。在对N末端前B型利钠尿肽（NT-proBNP）进行额外调整以建立既定的风险预测指标后，基线（赔率[OR] 1.25； P = .03）和48-72小时（OR 1.43； P） = .001）cTnI与出院前死亡或HF恶化的较高风险相关。但是，只有30天的cTnI与180天的死亡相关（危险比1.25； P = .007）。 cTnI改变与临床结果之间没有曲线相关性。
结论：循环中的cTnI水平与ADHF的临床结局相关，但这些观察结果随着NT-proBNP的进一步调整而减弱。尽管它们可能代表了ADHF的一系列风险，但这些发现对治疗期间改变cTnI水平的含义提出了质疑。

BACKGROUND & AIMS: :Hafnium-doped titania (Hf/Ti = 0.01; 0.03; 0.05) had been facilely synthesized via a template sol-gel method on carbon fibre. Physico-chemical properties of the as-synthesized materials were characterized by X-ray diffraction, Raman spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis, scanning transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetry analysis and Brunauer-Emmett-Teller measurements. It was confirmed that Hf4+ substitute in the Ti4+ sites, forming Ti1-x Hf x O2 (x = 0.01; 0.03; 0.05) solid solutions with an anatase crystal structure. The Ti1-x Hf x O2 materials are hollow microtubes (length of 10-100 µm, outer diameter of 1-5 µm) composed of nanoparticles (average size of 15-20 nm) with a surface area of 80-90 m2 g-1 and pore volume of 0.294-0.372 cm3 g-1. The effect of Hf ion incorporation on the electrochemical behaviour of anatase TiO2 in the Li-ion battery anode was investigated by galvanostatic charge/discharge and electrochemical impedance spectroscopy. It was established that Ti0.95Hf0.05O2 shows significantly higher reversibility (154.2 mAh g-1) after 35-fold cycling at a C/10 rate in comparison with undoped titania (55.9 mAh g-1). The better performance offered by Hf4+ substitution of the Ti4+ into anatase TiO2 mainly results from a more open crystal structure, which has been achieved via the difference in ionic radius values of Ti4+ (0.604 Å) and Hf4+ (0.71 Å). The obtained results are in good accord with those for anatase TiO2 doped with Zr4+ (0.72 Å), published earlier. Furthermore, improved electrical conductivity of Hf-doped anatase TiO2 materials owing to charge redistribution in the lattice and enhanced interfacial lithium storage owing to increased surface area directly depending on the Hf/Ti atomic ratio have a beneficial effect on electrochemical properties.

背景与目标： ：通过模板溶胶-凝胶法在碳纤维上容易地合成了掺af的二氧化钛（Hf / Ti ＝ 0.01； 0.03； 0.05）。通过X射线衍射，拉曼光谱，扫描电子显微镜，能量色散X射线分析，扫描透射电子显微镜，X射线光电子能谱，热重分析和Brunauer-Emmett表征了所合成材料的物理化学性质。 -出纳员测量。确认在Ti4位上存在Hf4替代物，形成Ti1-x Hf
X
具有锐钛矿型晶体结构的O2（x == 0.01; 0.03; 0.05）固溶体。 Ti1-x Hf
X
O2材料是中空微管（长度为10-100μm，外径为1-5μm），由纳米颗粒（平均尺寸为15-20μnm）组成，表面积为80-90μm2μg-1，孔体积为0.294 -0.372 cm3 g-1。通过恒电流充/放电和电化学阻抗谱研究了Hf离子掺入对锐钛矿型TiO2在锂离子电池阳极中电化学行为的影响。已经确定，与未掺杂的二氧化钛（55.9 mAh g-1）相比，Ti0.95Hf0.05O2在以C / 10速率循环35倍后显示出更高的可逆性（154.2 mAh g-1）。 Hf4将Ti4替换为锐钛矿型TiO2所提供的更好性能，主要是由于晶体结构更开放，这是通过Ti4（0.604Å）和Hf4（0.71Å）的离子半径值的差异实现的。所得结果与先前公布的掺杂Zr4（0.72Å）的锐钛矿型TiO2的结果非常吻合。此外，由于Hf / Ti原子比直接取决于Hf / Ti原子比，由于在晶格中电荷的重新分布，改善了Hf掺杂的锐钛矿型TiO2材料的电导率以及由于增加了表面积而增加了界面锂存储。

BACKGROUND & AIMS: :Anemia is common in patients with chronic heart failure (HF), with a prevalence ranging from 10% to 56%, and may be a risk factor for poor outcomes. Anemia in HF remains poorly understood, with significant gaps in its impact on health-related quality of life (HRQoL), with most studies in HF being retrospective or from registries. The purpose of this study was to explore the relation of hemoglobin (Hgb) with HRQoL and training-induced changes in HRQoL in a cohort of patients in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION). Using data from HF-ACTION, a randomized controlled trial of exercise training in patients with HF and low left ventricular ejection fractions, HRQoL was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 3 and 12 months, and annually up to 4 years. Treatment group effects on HRQoL were estimated using linear mixed models according to the intention-to-treat principle. It was hypothesized that baseline Hgb would be correlated with baseline KCCQ scales and that Hgb would moderate the beneficial effect of exercise training on HRQoL. Hgb level was not significantly correlated with baseline HRQoL. Baseline Hgb did not moderate the beneficial effect of exercise training on KCCQ overall or subscales relative to usual care. In conclusion, in the HF-ACTION cohort, there was no correlation with baseline Hgb and baseline HRQoL as measured by the KCCQ. In addition, the beneficial effects of HRQoL from exercise training were not modulated by baseline Hgb.

背景与目标： ：贫血在慢性心力衰竭（HF）患者中很常见，患病率从10％到56％不等，并且可能是不良预后的危险因素。 HF的贫血仍然知之甚少，它对健康相关的生活质量（HRQoL）的影响还存在很大差距，大多数HF的研究都是回顾性研究或来自注册机构。本研究的目的是探讨心力衰竭患者队列中血红蛋白（Hgb）与HRQoL和训练诱发的HRQoL变化的关系：运动训练（HF-ACTION）的对照研究结果。使用来自HF-ACTION的数据，这是一项针对HF和左心室射血分数低的患者进行的运动训练的随机对照试验，使用堪萨斯城心肌病问卷（KCCQ）在基线，3个月和12个月以及每年最多4个月测量HRQoL年。根据意向性治疗原则，使用线性混合模型评估治疗组对HRQoL的影响。假设基线Hgb与基线KCCQ量表相关，并且Hgb会减轻运动训练对HRQoL的有益作用。 Hgb水平与基线HRQoL没有显着相关。基线Hgb并未减轻运动训练对KCCQ整体或相对于常规护理的分量表的有益作用。总之，在HF-ACTION队列中，通过KCCQ测量的与基线Hgb和基线HRQoL没有相关性。此外，运动训练对HRQoL的有益作用并未受到基线Hgb的调节。

BACKGROUND & AIMS: AIMS:Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS:Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). CONCLUSION:Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

背景与目标： 目的：先前的研究显示右心室（RV）起搏的不良影响。但是，许多房室（AV）阻滞患者需要进行心室起搏（VP）。 PREVENT-HF研究探讨了在无晚期心力衰竭的AV阻滞中RV与双心室（BIV）起搏期间的左心室（LV）重塑。预先指定的PREVENT-HF德国子研究对运动能力和N末端脑钠素前体肽（NT-proBNP）进行了研究。
方法和结果：将预期VP≥80％的患者随机分为RV或BIV起搏组。终点为最大摄氧量（pVO2），无氧阈值下的摄氧量（VO2AT），通气效率（VE / VCO2）和logNT-proBNP。考虑交叉，进行了治疗意向（ITT）和治疗中（OT）协方差分析（ANCOVA）。运动测试包括44例（RV：25，BIV：19）和NT-proBNP 53例（RV：29，BIV：24）。 ITT分析显示pVO2的显着差异[ANCOVA效应2.83 mL / kg / min，置信区间（CI）0.83-4.91，P = 0.007]，VO2AT（ANCOVA效应2.14 mL / min / k，CI 0.14-4.15，P = 0.03）和VE / VCO2（ANCOVA效应-5.46，CI -10.79至-0.13，P = 0.04）支持BIV随机化。在OT分析中，pVO2的显着优势仍然存在，而VO2AT和VE / VCO2则显示出有利于BIV起搏的趋势。 LogNT-proBNP组之间没有差异。 （ITT：ANCOVA效应为0.008，CI -0.40至0.41，P ＝ 0.97； OT：ANCOVA效应为-0.03，CI -0.44至0.30，P ＝ 0.90）。
结论：我们的研究表明，对于没有晚期心力衰竭和房室传导阻滞的患者，BIV起搏比RV起搏在1年内可产生更好的运动能力。相反，我们未观察到NT-proBNP的显着变化。更大的试验将允许评估BIV起搏在房室传导阻滞中的临床实用性。 ClinicalTrials.gov标识符：NCT00170326。

BACKGROUND & AIMS: :Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) was a multicenter, randomized controlled trial designed to examine the safety and efficacy of aerobic exercise training versus usual care in 2,331 patients with systolic heart failure (HF). In HF-ACTION patients with rest transthoracic echocardiographic measurements, the predictive value of 8 Doppler echocardiographic measurements-left ventricular (LV) diastolic dimension, mass, systolic (ejection fraction) and diastolic (mitral valve peak early diastolic/peak late diastolic [E/A] ratio, peak mitral valve early diastolic velocity/tissue Doppler peak early diastolic myocardial velocity [E/E'] ratio, and deceleration time) function, left atrial dimension, and mitral regurgitation severity-was examined for a primary end point of all-cause death or hospitalization and a secondary end point of cardiovascular disease death or HF hospitalization. Also compared was the prognostic value of echocardiographic variables versus peak oxygen consumption (Vo(2)). Mitral valve E/A and E/E' ratios were more powerful independent predictors of clinical end points than the LV ejection fraction but less powerful than peak Vo(2). In multivariate analyses for predicting the primary end point, adding E/A ratio to a basic demographic and clinical model increased the C-index from 0.61 to 0.62, compared with 0.64 after adding peak Vo(2). For the secondary end point, 6 echocardiographic variables, but not the LV ejection fraction or left atrial dimension, provided independent predictive power over the basic model. The addition of E/E' or E/A to the basic model increased the C-index from 0.70 to 0.72 and 0.73, respectively (all p values <0.0001). Simultaneously adding E/A ratio and peak Vo(2) to the basic model increased the C-index to 0.75 (p <0.0005). No echocardiographic variable was significantly related to the change from baseline to 3 months in exercise peak Vo(2). In conclusion, the addition of echocardiographic LV diastolic function variables improves the prognostic value of a basic demographic and clinical model for cardiovascular disease outcomes.

背景与目标： 心力衰竭：运动训练的对照试验研究结果（HF-ACTION）是一项多中心，随机对照试验，旨在检查有氧运动训练与常规护理相比对2331例收缩期心力衰竭（HF）患者的安全性和有效性。在进行静息经胸超声心动图测量的HF-ACTION患者中，8种多普勒超声心动图测量的预测价值-左心室（LV）舒张大小，质量，收缩压（射血分数）和舒张压（二尖瓣峰值舒张早期/峰值舒张末期[E / A]比，二尖瓣舒张早期峰值速度/组织多普勒峰值舒张早期心肌速度[E / E']比和减速时间）功能，左心房尺寸和二尖瓣关闭不全的严重程度-被作为所有患者的主要终点-导致死亡或住院，以及心血管疾病死亡或HF住院的次要终点。还比较了超声心动图变量与峰值耗氧量（Vo（2））的预后价值。二尖瓣E / A和E / E'比比LV射血分数更有效的临床终点独立预测因子，但不如峰值Vo（2）强大。在用于预测主要终点的多变量分析中，将E / A比添加到基本人口统计和临床模型中后，C指数从0.61增至0.62，而在增加峰值Vo（2）之后则为0.64。对于次要终点，6个超声心动图变量而不是LV射血分数或左心房尺寸对基本模型提供了独立的预测能力。在基本模型中添加E / E'或E / A会使C指数分别从0.70增加到0.72和0.73（所有p值<0.0001）。同时将E / A比和峰值Vo（2）添加到基本模型中会使C指数增加到0.75（p <0.0005）。没有超声心动图变量与运动峰值Vo（2）从基线到3个月的变化显着相关。总之，超声心动图左室舒张功能变量的增加改善了心血管疾病预后的基本人口统计学和临床​​模型的预后价值。

BACKGROUND & AIMS: AIMS:The study assessed 4-year outcomes of intramyocardial injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic heart failure. METHODS AND RESULTS:The MSC-HF trial was a randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to intramyocardial injections of MSCs or placebo. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography. Sixty patients aged 30-80 years with ischaemic heart failure, New York Heart Association class II-III, left ventricular ejection fraction (LVEF) <45% and no further treatment options were randomized. Patients were followed clinically for 12 months and in addition 4-year data of hospitalizations and survival were retrieved. After 12 months, LVESV was significantly reduced in the MSC group and not in the placebo group, with difference between groups of 17.0 ± 16.2 mL (95% confidence interval 8.3-25.7, P = 0.0002). There were also significant improvements in LVEF of 6.2% (P < 0.0001), stroke volume of 16.1 mL (P < 0.0001) and myocardial mass (P = 0.009) between groups. A significant dose-response effect was also observed. Moreover, a significant reduction in the amount of scar tissue and quality of life score in the MSC group but not in the placebo group was observed. After 4 years, there were significantly fewer hospitalizations for angina in the MSC group and otherwise no differences in hospitalizations or survival. No side effects were identified. CONCLUSIONS:Intramyocardial injections of autologous bone marrow-derived MSCs improved myocardial function and myocardial mass in patients with ischaemic heart failure.

背景与目标： 目的：该研究评估了缺血性心力衰竭患者心肌内注射自体骨髓源间充质基质细胞（MSC）的4年结果。
方法和结果：MSC-HF试验是一项随机，双盲，安慰剂对照试验。患者按2：1随机接受心肌内注射MSC或安慰剂。主要终点是通过磁共振成像或计算机断层扫描测量的左心室收缩末期容积（LVESV）的变化。 60名年龄在30-80岁的缺血性心力衰竭患者，纽约心脏协会II-III级，左心室射血分数（LVEF）<45％，并且没有进一步的治疗选择。临床上对患者进行了12个月的随访，此外还检索了4年的住院和生存数据。 12个月后，MSC组而非安慰剂组LVESV显着降低，两组之间的差异为17.0±16.2mL（95％置信区间8.3-25.7，P = 0.0002）。两组之间的LVEF显着改善（6.2％（P <0.0001），中风量16.1 mL（P <0.0001）和心肌质量（P = 0.009）。还观察到显着的剂量反应作用。此外，在MSC组中观察到疤痕组织的数量和生活质量得分显着降低，而在安慰剂组中则没有观察到。四年后，MSC组的心绞痛住院率显着降低，否则住院率或生存率没有差异。没有发现副作用。
结论：心肌内注射自体骨髓源性间充质干细胞可改善缺血性心力衰竭患者的心肌功能和心肌质量。

BACKGROUND & AIMS: :Background Data comparing outcomes in heart failure (HF) across Asia are limited. We examined regional variation in mortality among patients with HF enrolled in the ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry with separate analyses for those with reduced ejection fraction (EF; <40%) versus preserved EF (≥50%). Methods and Results The ASIAN-HF registry is a prospective longitudinal study. Participants with symptomatic HF were recruited from 46 secondary care centers in 3 Asian regions: South Asia (India), Southeast Asia (Thailand, Malaysia, Philippines, Indonesia, Singapore), and Northeast Asia (South Korea, Japan, Taiwan, Hong Kong, China). Overall, 6480 patients aged >18 years with symptomatic HF were recruited (mean age: 61.6±13.3 years; 27% women; 81% with HF and reduced rEF). The primary outcome was 1-year all-cause mortality. Striking regional variations in baseline characteristics and outcomes were observed. Regardless of HF type, Southeast Asians had the highest burden of comorbidities, particularly diabetes mellitus and chronic kidney disease, despite being younger than Northeast Asian participants. One-year, crude, all-cause mortality for the whole population was 9.6%, higher in patients with HF and reduced EF (10.6%) than in those with HF and preserved EF (5.4%). One-year, all-cause mortality was significantly higher in Southeast Asian patients (13.0%), compared with South Asian (7.5%) and Northeast Asian patients (7.4%; P<0.001). Well-known predictors of death accounted for only 44.2% of the variation in risk of mortality. Conclusions This first multinational prospective study shows that the outcomes in Asian patients with both HF and reduced or preserved EF are poor overall and worst in Southeast Asian patients. Region-specific risk factors and gaps in guideline-directed therapy should be addressed to potentially improve outcomes. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01633398.

背景与目标： ：在亚洲比较心力衰竭（HF）结果的背景数据有限。我们通过对射血分数降低（EF; <40％）相对于保留EF（≥50％）的那些进行单独分析，研究了ASIAN-HF（亚洲心力衰竭亚洲猝死）登记的HF患者的死亡率区域差异。 。方法和结果ASIAN-HF登记册是一项前瞻性纵向研究。有症状性HF的参与者来自亚洲三个地区的46个二级保健中心：南亚（印度），东南亚（泰国，马来西亚，菲律宾，印度尼西亚，新加坡）和东北亚（韩国，日本，台湾，香港，中国）。总共招募了6480例> 18岁的有症状HF患者（平均年龄：61.6±13.3岁; 27％的女性; 81％的HF和rEF降低）。主要结局为1年全因死亡率。观察到基线特征和结果的惊人区域差异。不管是哪种类型的HF，尽管比东北亚参与者年轻，但东南亚人的合并症负担特别重，尤其是糖尿病和慢性肾脏疾病。整个人群一年的全因粗略死亡率为9.6％，与HF和EF保留的患者（5.4％）相比，HF和EF降低的患者（10.6％）更高。东南亚患者（13.0％）的一年全因死亡率显着高于南亚（7.5％）和东北亚患者（7.4％； P <0.001）。众所周知的死亡预测因素仅占死亡风险变化的44.2％。结论这项第一项跨国前瞻性研究表明，亚洲的HF和EF降低或保留的患者总体效果较差，在东南亚患者中最差。应解决特定地区的风险因素和指导性治疗中的差距，以潜在地改善疗效。临床试验注册网址：https：//www.clinicaltrials.gov/。唯一标识符：NCT01633398。

BACKGROUND & AIMS: BACKGROUND:The PARADIGM-HF trial showed that sacubitril-valsartan - an angiotensin receptor-neprilysin inhibitor (ARNI) - is more effective than enalapril for some patients with heart failure. However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established. METHODS:We made secondary analysis of patients (n = 4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from Sahlgrenska University Hospital/Östra Hospital, Sweden during 2005-2016. The eligibility of the PARADIGM-HF trial in the real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF population. Patients were judged to be fully eligible for the PARADIGM-HF trial if they completely met the inclusion and exclusion criteria, and partially eligible if they did not stay on target dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), despite their having been treated with ACEI/ARB for at least 6 months. RESULTS:Among patients who had heart failure with reduced left ventricular ejection fraction (≤40%) (HFrEF) (n = 2165), 653 (30%) and 958 (44%) patients were fully and partially compatible with PARADIGM-HF criteria, respectively. In both fully and partially eligible groups, patients were more male. Despite those fully eligible patients being younger (77.6 ± 12.7 vs. 84.0 ± 13.7 years) than noneligible patients, they were much older than in the PARADIGM-HF trial. Moreover, those fully eligible patients had lower all-cause mortality compared with both partially and noneligible patients. However, both fully and partially eligible patients had higher all-cause mortality than that in the PARADIGM-HF trial. CONCLUSION:In a real-world outpatient clinical setting, around 1/3-1/2 of HFrEF were eligible for treatment of Sac/Val except that they are older, sicker, and carry higher risk for all-cause mortality than the PARADIGM-HF trial population.

背景与目标： 背景：PARADIGM-HF试验显示，对于一些心力衰竭患者，沙比特比尔-缬沙坦（一种血管紧张素受体-中性溶酶抑制剂（ARNI））比依那普利更有效。但是，PARADIGM-HF研究是否适合实际的心力衰竭人群的资格还没有很好地确定。
方法：我们对2005-2016年间瑞典Sahlgrenska大学医院/Östra医院的瑞典心力衰竭登记处的前瞻性入组的心力衰竭患者（n = 4872）进行了二次分析。根据患者是否与PARADIGM-HF人群完全或部分兼容，研究了PARADIGM-HF试验在现实世界中的资格。如果患者完全符合纳入和排除标准，则被判断为完全符合PARADIGM-HF试验的条件，如果患者未继续接受血管紧张素转换酶抑制剂（ACEI）/血管紧张素受体阻滞剂（ARB）的目标剂量，则被部分评定为完全合格，尽管他们已经接受ACEI / ARB治疗至少6个月。
结果：在心力衰竭患者中，左心室射血分数降低（≤40％）（HFrEF）（n = 2165），653（30％）和958（44％）患者完全或部分符合PARADIGM-HF标准， 分别。在完全合格和部分合格的组中，患者均为男性。尽管那些完全合格的患者比不符合条件的患者年轻（77.6±12.7岁vs. 84.0±13.7岁），但他们的年龄比PARADIGM-HF试验的年龄大得多。此外，与部分和不合格患者相比，那些完全合格的患者的全因死亡率更低。但是，完全合格和部分合格的患者的全因死亡率均高于PARADIGM-HF试验。
结论：在现实的门诊临床环境中，约有1 / 3-1 / 2的HFrEF有资格接受Sac / Val的治疗，但它们比PARADIGM- HF试验人群。

BACKGROUND & AIMS: INTRODUCTION:Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. AIM:ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. METHODS:ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. CONCLUSION:The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality.

背景与目标： 简介：两种类型的睡眠障碍呼吸（SDB），阻塞性和中枢性睡眠呼吸暂停（分别为OSA和CSA）在心力衰竭和射血分数降低（HFrEF）的患者中都很常见。在此类患者中，SDB与心血管疾病的发病率和死亡率增加相关，但尚不确定在此类患者中通过适应性伺服通气（ASV）治疗SDB是否会降低发病率和死亡率。
目的：ADVENT-HF旨在评估ASV治疗SDB对HFrEF患者的发病率和死亡率的影响。
方法：ADVENT-HF是一项多中心，多国，随机，平行分组，开放标签的试验，对仅HFrEF的标准药物治疗终点与HFrEF和SDB患者的ASV进行盲法评估。有HFrEF病史的患者接受超声心动图和多导睡眠图检查。左心室射血分数≤45％且SDB（呼吸暂停－呼吸不足指数≥15）的患者符合条件。 SDB分为≥50％阻塞事件的OSA或> 50％中心事件的CSA。患有OSA的人白天不能有过多的嗜睡（Epworth分数≤10）。然后将患者随机接受或不接受ASV。主要结果是所有原因的死亡率，心血管疾病的住院人数，需要抗凝但不需要住院的新发房颤的综合因素，以及从植入式心脏复律除颤器中排出的适当药物不会导致最大随访期间的住院续航时间为5年。
结论：ADVENT-HF试验将有助于确定ASV治疗HFrEF患者的SDB是否能改善发病率和死亡率。

BACKGROUND & AIMS: :The MERIT-HF study was a randomized, double-blind, placebo-controlled trial with a single-blind, two-week placebo run-in period. There were two primary objectives: total mortality; and the combined endpoint of total mortality or all-cause hospitalizations (time to first event). Several other combined endpoints were also predefined, as were number of hospitalizations due to heart failure and other cardiovascular causes, withdrawal of study medicine due to all causes, and due to worsening heart failure, and change in NYHA class. The effect on Quality of Life was assessed in a substudy. The major inclusion criteria were symptomatic heart failure for at least 3 months corresponding to NYHA class II-IV; and a left ventricular ejection fraction of 0.40 or less in 40 to 80 year old men and women. The patients had to be on optimal treatment for at least 2 weeks prior to randomization, defined in principle as any combination of diuretics and an ACE inhibitor. The recommended starting dose was half a 25 mg tablet of metoprolol CR/Zok once daily in patients in NYHA functional class III-IV, and one 25 mg tablet once daily in patients in NYHA class II. It was recommended to double the dose after each 2-week period in order to reach the highest tolerated dose aiming for a target dose level of 200 mg once daily of metoprolol CR/Zok or placebo. This dosage regimen could be modified according to the judgement of the investigator. Randomization began on February 14, 1997, and the last patient was randomized April 14, 1998. 1990 patients were randomized to metoprolol CR/Zok and 2001 to placebo. The International Steering Committee stopped the study by October 31, 1998, upon recommendation from the Independent Safety Committee. The second pre-planned interim analysis (50% point) had shown that the pre-defined criterion for termination of the study was met and exceeded. The mean follow-up time was 1 year.

背景与目标： ：MERIT-HF研究是一项随机，双盲，安慰剂对照试验，有一个单盲，两周安慰剂磨合期。有两个主要目标：总死亡率；以及总死亡率或全因住院（首次事件发生的时间）的综合终点。还预定义了其他几个组合的终点，包括因心力衰竭和其他心血管原因导致的住院治疗次数，由于所有原因，由于心力衰竭加重而退出研究药物以及NYHA等级变化的原因。在一项子研究中评估了对生活质量的影响。主要纳入标准为症状性心力衰竭至少3个月，相当于NYHA II-IV级；在40至80岁的男性和女性中，左心室射血分数在0.40以下。患者必须在随机分组前至少2周接受最佳治疗，原则上定义为利尿剂和ACE抑制剂的任何组合。建议的起始剂量是NYHA功能性III-IV级患者每天25 mg片剂美托洛尔CR / Zok的一半，而NYHA II级患者则每日一次25 mg片剂。建议在每两周后加倍剂量，以达到最高耐受剂量，目标是每天一次美托洛尔CR / Zok或安慰剂的目标剂量为200 mg。该剂量方案可以根据研究者的判断进行修改。随机分组始于1997年2月14日，最后一名患者被随机分组​​于1998年4月14日。1990年患者被随机分组​​接受美托洛尔CR / Zok治疗，2001年患者被随机给予安慰剂治疗。根据独立安全委员会的建议，国际指导委员会在1998年10月31日之前停止了该研究。第二次预先计划的中期分析（50％点）表明，已经达到并超出了终止研究的预定标准。平均随访时间为1年。

BACKGROUND & AIMS: BACKGROUND:Current inotropes have inodilator properties and, although are frequently used in acute heart failure syndromes, do not improve outcomes, likely from reduction in systolic blood pressure and increasing in arrhythmias, causing worsened myocardial ischemia and end-organ damage. Istaroxime is a novel agent that, in animal models, has both inotropic (inhibition of the Na/K ATPase channel) and lusitropic (stimulation of sarcoplasmic reticulum calcium ATPase activity) effects. HORIZON-HF is designed to test the hypothesis that istaroxime is effective in improving central hemodynamics and left ventricular (LV) function, without lowering systolic blood pressure, increasing heart rate, and worsening renal function or myocardial necrosis. METHODS AND RESULTS:This was a phase 2, randomized, double-blind, placebo-controlled, multicenter dose escalation exploratory study comparing 3 different doses of istaroxime to placebo in patients with LV systolic dysfunction (LV ejection fraction

BACKGROUND & AIMS: :The PARAGON-HF clinical trial suggested that sacubitril/valsartan may become a treatment option for particular subgroups of patients with heart failure and preserved ejection fraction (HFpEF). However, the proportion of real-world HFpEF patients who are theoretically superimposable with the PARAGON-HF population is yet unknown. The present study was performed to define the proportion of real-world PARAGON-HF-like patients and to describe their clinical characteristics and long-term prognosis in comparison with those who would not meet PARAGON-HF criteria. We systematically applied PARAGON-HF inclusion and exclusion criteria to a total of 427 HFpEF patients who have been participating in a prospective national registry between December 2010 and December 2019. In total, only 170 (39.8%) registry patients were theoretically eligible for PARAGON-HF. Patients not meeting inclusion criteria (41.0%) were less impaired with respect to exercise capacity (median 6-min walk distance: 385 m (IQR: 300-450) versus 323 m (IQR: 240-383); p < 0.001) had lower pulmonary pressures (mean pulmonary artery pressure (mPAP): 31.2 mmHg, standard deviation (SD): ±10.2 versus 32.8 mmHg, SD: ±9.7; p < 0.001) and better outcomes (log-rank: p < 0.001) as compared to the PARAGON-like cohort. However, patients theoretically excluded from the trial (19.2%) were those with most advanced heart failure symptoms (median 6-min walk test: 252 m (IQR: 165-387); p < 0.001), highest pulmonary pressures (mPAP: 38.2 mmHg, SD: ±12.4; p < 0.001) and worst outcome (log-rank: p = 0.037). We demonstrate here that < 40% of real-world HFpEF patients meet eligibility criteria for PARAGON-HF. We conclude that despite reasons for optimism after PARAGON-HF, a large proportion of HFpEF patients will remain without meaningful treatment options.

背景与目标： ：PARAGON-HF临床试验表明，沙比特比/缬沙坦可能成为心力衰竭和射血分数保留（HFpEF）的特定亚组患者的治疗选择。然而，尚无理论上可与PARAGON-HF人群叠加的现实世界中HFpEF患者的比例。进行本研究的目的是确定现实世界中类似PARAGON-HF的患者的比例，并与不符合PARAGON-HF标准的患者进行比较，以描述其临床特征和长期预后。我们系统地将PARAGON-HF纳入和排除标准应用于2010年12月至2019年12月之间参加前瞻性国家注册的427名HFpEF患者。理论上，总共只有170名（39.8％）注册患者符合PARAGON-高频不符合入选标准的患者（41.0％）的运动能力受损程度较小（中位6分钟步行距离：385 m（IQR：300-450）与323 m（IQR：240-383）; p <0.001）较低的肺动脉压（平均肺动脉压（mPAP）：31.2 mmHg，标准偏差（SD）：±10.2与32.8 mmHg，SD：±9.7; p <0.001）和更好的结果（log-rank：p <0.001）像PARAGON一样的人群。但是，理论上从该试验中排除的患者（19.2％）是那些具有最严重的心力衰竭症状（中位6分钟步行测试：252 m（IQR：165-387）； p <0.001），最高肺动脉压（mPAP：38.2）的患者。 mmHg，SD：±12.4； p <0.001）和最差的结果（对数秩：p = 0.037）。我们在此证明，现实世界中少于40％的HFpEF患者符合PARAGON-HF的入选标准。我们得出结论，尽管有理由在PARAGON-HF后感到乐观，但仍有很大一部分HFpEF患者没有有意义的治疗选择。