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。

BACKGROUND & AIMS: OBJECTIVES:This study sought to evaluate the efficacy and safety of sacubitril/valsartan according to dose level achieved in the PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial. BACKGROUND:In patients hospitalized for acute decompensated heart failure (ADHF), in-hospital initiation and continuation of sacubitril/valsartan as compared with enalapril is well tolerated, achieves a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), and reduces the risk of cardiovascular death or rehospitalization for HF through 8 weeks. However, not all patients achieve the target dose of sacubitril/valsartan, and its efficacy and safety in such patients are of interest. METHODS:PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan versus enalapril in 881 patients stabilized during hospitalization for ADHF. Blinded study medication was administered for 8 weeks, with initial dosing selected based on the systolic blood pressure at randomization and titrated toward a target of sacubitril/valsartan 97/103 mg twice daily, or enalapril 10 mg twice daily, with an algorithm based on systolic blood pressure and the investigator's assessment of tolerability. RESULTS:At 4 weeks, 199 (55%) patients allocated to sacubitril/valsartan and 211 (60%) patients allocated to enalapril were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. There was no heterogeneity across dose levels in the effect of sacubitril/valsartan on the reduction in NT-proBNP (pinteraction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (pinteraction = 0.42), or the pre-specified adverse events of special interest through 8 weeks. CONCLUSIONS:In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).

背景与目标： 目的：本研究旨在根据PIONEER-HF（急性心力衰竭发作稳定的患者中沙库比特/缬沙坦与依那普利对NT-proBNP的影响比较）评估的剂量水平来评估沙库比特/缬沙坦的疗效和安全性。 。
背景：在住院治疗急性失代偿性心力衰竭（ADHF）的患者中，与依那普利相比，在医院内开始使用沙必比尔/缬沙坦的起始和持续耐受性良好，N端前B型利钠肽（NT- proBNP），并通过8周的时间降低因心衰导致的心血管死亡或再次住院的风险。但是，并非所有患者都能达到沙必比/缬沙坦的目标剂量，因此在此类患者中其疗效和安全性值得关注。
方法：PIONEER-HF是一项沙比特利/缬沙坦与依那普利的随机，双盲，主动对照试验，用于在住院期间稳定的881例ADHF患者中进行。盲法研究药物给药8周，根据随机选择的收缩压选择初始剂量，并以基于收缩压的算法每天两次将沙比特利/缬沙坦97/103 mg或滴定的依那普利10 mg滴定至目标血压和研究者对耐受性的评估。
结果：在第4周，分配了sacubitril / valsartan的199名患者（55％）和分配了enalapril的211名患者（60％）分配了目标剂量。在每个剂量水平下，两个治疗组的基线特征相似。沙比特比/缬沙坦对减少NT-proBNP的影响（交互作用= 0.69），心血管死亡或因心力衰竭而重新住院（交互作用= 0.42）或预先指定的不良事件的影响在各个剂量水平上均无异质性直到8周的特殊兴趣。
结论：在血液动力学稳定的ADHF患者中，沙比特利/缬沙坦的疗效和安全性在各个剂量水平上通常是一致的。沙库比特/缬沙坦与依那普利对急性心力衰竭发作稳定的患者对NT-proBNP影响的比较[PIONEER-HF]； NCT02554890）。

BACKGROUND & AIMS: BACKGROUND:Symptoms and signs of heart failure (HF) are the most common reasons for admission to hospital for acute HF (AHF) and are used routinely throughout admission to assess the severity of disease and response to therapy. METHODS AND RESULTS:The data were collected in The Sub-Saharan Africa Survey on Heart Failure (THESUS-HF) study, a prospective, multicenter, observational survey of AHF from 9 countries in sub-Saharan Africa. A total of 1006 patients, ≥12 years of age, hospitalized for AHF were recruited. Symptoms and signs of HF and changes in dyspnea and well-being, relative to admission, were assessed at entry and on days 1, 2, and 7 (or on discharge if earlier) and included oxygen saturation, degree of edema and rales, body weight, and level of orthopnea. The patient determined dyspnea and general well-being, whereas the physician determined symptoms and signs of HF, as well as improvements in vital sign measurement, throughout the admission. After multivariable adjustment, baseline rales and changes to day 7 or discharge in general well-being predicted death or HF hospitalization through day 60, and baseline orthopnea, edema, rales, oxygen saturation, and changes to day 7 or on discharge in respiratory rate and general well-being were predictive of death through day 180. CONCLUSIONS:In AHF patients in sub-Saharan Africa, symptoms and signs of HF improve throughout admission, and simple assessments, including edema, rales, oxygen saturation, respiratory rate, and asking the patient about general well-being, are valuable tools in patients' clinical assessment.

背景与目标： 背景：症状和心力衰竭（HF）的症状是急性HF（AHF）入院的最常见原因，在入院期间通常用于评估疾病的严重程度和对治疗的反应。
方法和结果：数据收集自撒哈拉以南非洲心力衰竭调查（THESUS-HF）研究，该研究来自撒哈拉以南非洲9个国家的AHF的前瞻性，多中心，观察性调查。总共招募了1006名≥12岁的AHF住院患者。在入院时，入院后第1、2和7天（或出院时，如较早）评估HF的症状和体征以及呼吸困难和幸福感的变化，包括氧饱和度，水肿和ra音程度，身体体重和口气水平。患者在整个入院期间确定呼吸困难和总体健康状况，而医生确定HF的症状和体征以及生命体征测量的改善。经过多变量调整后，基线罗音变化至第7天，或出院一般情况下可预测到第60天死亡或HF住院，基线通气，浮肿，罗勒，血氧饱和度，以及到第7天或出院时呼吸频率和总体健康状况可预测到180天的死亡人数。
结论：在撒哈拉以南非洲的AHF患者中，HF的症状和体征在整个入院过程中都会改善，简单的评估（包括水肿、,音，血氧饱和度，呼吸频率以及询问患者的总体健康状况）是患者的重要工具临床评估。

BACKGROUND & AIMS: OBJECTIVES:The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). BACKGROUND:Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. METHODS:A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period. RESULTS:The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011). CONCLUSIONS:Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.

背景与目标： 目的：本研究的目的是比较丁苯达洛尔和琥珀酸美托洛尔在维持遗传性心力衰竭（HF）并伴有房颤（AF）的人群中维持窦性心律的有效性。
背景：丁三醇是一种β受体阻滞剂，其独特的药理特性可为射血分数降低（HFrEF）的具有β1-肾上腺素能受体（ADRB1）Arg389Arg基因型的HF患者提供更大的益处。
方法：将267名HFrEF患者（左心室射血分数（LVEF）<0.50），症状性房颤和ADRB1 Arg389Arg基因型随机分配为1：1随机接受丁三醇或美托洛尔治疗，并调高至目标剂量。在24周内通过心电图（ECG）评估了房颤或房扑（AFL）或全因死亡率（ACM）的主要终点。
结果：主要终点的危险比（HR）为1.01（95％置信区间[CI]：0.71至1.42），但是在几个亚组中观察到了丁三醇的获益趋势。精确的治疗表型表明，从最初诊断为AF和HF到随机化的时间间隔，以及相对于最初HF诊断的AF发作，对丁三醇的反应不同。在队列中首次被诊断为AF和HF小于随机分组的人群中，AF发作在HF之前不超过2年（n = 196），HR为0.54（95％CI：0.33至0.87; p = 0.011）。
结论：与美托洛尔治疗相比，药理学上指导的丁三醇治疗并未降低AF / AFL或ACM的复发率，但确定了值得在未来3期试验中进行进一步研究的人群。

BACKGROUND & AIMS: BACKGROUND:The Needs Assessment Tool: Progressive Disease - Heart Failure (NAT:PD-HF) was developed to identify and triage palliative care needs in patients with chronic heart failure. A Dutch version is currently lacking. AIMS:The aim of this study was to investigate the feasibility and acceptability of a Dutch NAT:PD-HF in chronic heart failure outpatients; and to gain preliminary data regarding the effect of the NAT:PD-HF on palliative care referral, symptoms, health status, care dependency, caregiver burden and advance directives. METHODS:A mixed methods study including 23 outpatients with advanced chronic heart failure and 20 family caregivers was performed. Nurses conducted patient consultations using a Dutch translation of the NAT:PD-HF and rated acceptability. Before this visit and 4 months later, symptoms, health status, performance status, care dependency, caregiver burden and recorded advance directives were assessed. A focus group with participating nurses discussed barriers and facilitators towards palliative care needs assessment. RESULTS:Acceptability was rated as 7 (interquartile range 6-7 points) on a 10-point scale. All patients had palliative care needs. In 48% actions were taken, including two patients referred to palliative care. Symptoms, performance status, care dependency, caregiver burden and advance directives were unchanged at 4 months, while health status deteriorated in patients completing follow-up ( n=17). Barriers towards palliative care needs assessment included feeling uncomfortable to initiate discussions and concerns about the ability to address palliative care needs. CONCLUSIONS:The NAT:PD-HF identified palliative care needs in all participants, and triggered action to address these in half. However, training in palliative care communication skills as well as palliative care interventions should accompany the introduction of a palliative care needs assessment tool. NETHERLANDS NATIONAL TRIAL REGISTER (NTR):5616. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5616.

背景与目标： 背景：需求评估工具：进行性疾病-心力衰竭（NAT：PD-HF）被开发用于识别和分类慢性心力衰竭患者的姑息治疗需求。当前缺少荷兰语版本。
目的：本研究的目的是调查荷兰NAT：PD-HF在慢性心力衰竭门诊患者中的可行性和可接受性。并获得有关NAT：PD-HF对姑息治疗转诊，症状，健康状况，护理依赖性，护理人员负担和预先指示的影响的初步数据。
方法：采用混合方法研究，包括23名晚期慢性心力衰竭门诊患者和20名家庭护理人员。护士使用NAT：PD-HF的荷兰语翻译和额定可接受性进行了患者咨询。在这次就诊之前和4个月后，评估了症状，健康状况，表现状况，护理依赖性，护理人员负担和记录的预先医疗指示。一个由参与护士组成的焦点小组讨论了姑息治疗需求评估的障碍和促进者。
结果：可接受性以10分制为7分（四分位数范围6-7分）。所有患者都有姑息治疗需求。在48％的患者中采取了行动，包括两名接受姑息治疗的患者。症状，表现状态，护理依赖性，护理人员负担和提前指示在4个月时未发生变化，而完成随访的患者的健康状况则有所恶化（n = 17）。姑息治疗需求评估的障碍包括，对于进行讨论和对解决姑息治疗需求的能力感到不自在。
结论：NAT：PD-HF确定了所有参与者的姑息治疗需求，并触发了行动来解决这些需求。但是，应该引入姑息治疗需求评估工具，以提供有关姑息治疗沟通技能的培训以及姑息治疗干预措施。
荷兰国家试验注册（NTR）：5616。 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5616。

BACKGROUND & AIMS: :In this work, specific topics will be covered in order to verify an effective, routine application of ion chromatography as a suitable and approved technique for emission monitoring in the determination of HF, HCl, NOx and SOx on stationary emission. A review of the analytical methods as proposed by recent updates in Italian environmental law and the problems encountered in the application of this method, such us the interference due to high level of carbonate, high hydroxides concentration particularly on SOx and NOx absorbing solution, are considered in the present work. The sample treatments before the IC analysis, this to reduce the matrix interference due to the strong basic solutions used to monitor different stationary emissions, are also examined. Some modifications in sampling are explored to find more suitable conditions for the IC analysis.

背景与目标： ：在本工作中，将涵盖特定主题，以验证离子色谱法在确定固定排放物上的HF，HCl，NOx和SOx的排放中作为一种合适且已批准的排放物监测技术的常规应用。考虑了对意大利环境法最新更新中提出的分析方法的回顾以及该方法应用中遇到的问题，例如碳酸盐含量高，氢氧化物浓度高（特别是SOx和NOx吸收溶液）引起的干扰在目前的工作中。在IC分析之前，还对样品处理进行了测试，这是由于使用了用于监视不同固定辐射的强大基本解决方案，从而减少了基质干扰。探索采样中的一些修改以找到更适合IC分析的条件。

BACKGROUND & AIMS: :We conducted a high-throughput investigation of the fundamental properties of (Mg,Hf)xAl1-xN thin films (0 < x < 0.24) aiming for developing high-performance AlN-based piezoelectric materials. For the high-throughput investigation, we prepared composition-gradient (Mg,Hf)xAl1-xN films grown on a Si(100) substrate at 600 °C by cosputtering AlN and MgHf targets. To measure the properties of the various compositions at different positions within a single sample, we used characterization techniques with spatial resolution. X-ray diffraction (XRD) with a beam spot diameter of 1.0 mm verified that Mg and Hf had substituted into the Al sites and caused an elongation of the c-axis of AlN from 5.00 Å for x = 0 to 5.11 Å for x = 0.24. In addition, the uniaxial crystal orientation and high crystallinity required for piezoelectric materials to be used as application devices were confirmed. The piezoelectric response microscope indicated that this c-axis elongation increased the piezoelectric coefficient almost linearly from 1.48 pm/V for x = 0 to 5.19 pm/V for x = 0.24. The dielectric constants of (Mg,Hf)xAl1-xN were investigated using parallel plate capacitor structures with ∼0.07 mm2 electrodes and showed a slight increase by substitution. These results verified that (Mg,Hf)xAl1-xN is a promising material for piezoelectric-based application devices, especially for vibrational energy harvesters.

背景与目标： ：我们对（Mg，Hf）xAl1-xN薄膜（0

BACKGROUND & AIMS: With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of heart failure, especially lethal arrhythmias and sudden cardiac death, focus has returned to the potential benefits of beta-adrenergic blockade. In patients with myocardial infarction and left ventricular (LV) dysfunction, particularly those prone to life-threatening arrhythmias, beta-blocker therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of angiotensin-converting enzyme (ACE) inhibition, beta blockade has improved cardiac function and LV contractility in nonischemic heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the Metoprolol in Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency Bisoprolol Study (CIBIS) found beta blockade to be associated with decreased mortality rates in patients with nonischemic heart failure. Of the 3 large randomized mortality trials now under way, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) is specifically designed to investigate the effects of beta blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic heart failure. Unresolved issues to be addressed include whether(1) beta-blocker therapy in heart failure can improve survival and/or reduce the incidence of sudden cardiac death; (2) beta blockade is equally effective in ischemic and nonischemic heart failure; (3) any specific beta blocker may be better tolerated initially and cause fewer adverse effects; and (4) all beta blockers result in improved exercise tolerance and quality of life.

背景与目标： 随着对神经内分泌刺激对心力衰竭的不良后果（尤其是致命性心律不齐和心源性猝死）的影响有了更深入的了解，人们的注意力已经回到了β-肾上腺素能阻滞的潜在益处。在患有心肌梗塞和左心室（LV）功能障碍的患者中，尤其是那些容易危及生命的心律不齐的患者，β受体阻滞剂疗法与心律不齐的发生率较低和存活率提高相关。即使在没有血管紧张素转换酶（ACE）抑制的情况下，β阻滞剂也可改善非缺血性心力衰竭的心脏功能和左心室收缩能力，从而导致左心室舒张末期压力降低并改善临床状态。美托洛尔在扩张型心肌病（MDC）试验和心脏功能不全比索洛尔研究（CIBIS）中均发现，β阻滞剂与非缺血性心力衰竭患者的死亡率降低相关。在目前进行的3项大型随机死亡率试验中，美托洛尔CR / XL心力衰竭随机干预试验（MERIT-HF）是专门设计用于研究β受体阻滞剂作为患者ACE抑制的辅助药物时对总死亡率的影响缺血性或非缺血性心力衰竭。有待解决的尚未解决的问题包括：（1）心力衰竭中的β受体阻滞剂治疗是否可以提高生存率和/或减少心脏性猝死的发生率； （2）β受体阻滞剂在缺血性和非缺血性心力衰竭中均有效。 （3）任何特定的β受体阻滞剂最初可能耐受性更好，并且不良反应较少； （4）所有β受体阻滞剂均可改善运动耐力和生活质量。

BACKGROUND & AIMS: AIMS:The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. METHODS:We compared stratified (s ) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) ≤ 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age ≥ 70 years and EF ≤ 35%). RESULTS:The annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n = 2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P < 0.0001) and MERIT-HFs (n = 2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P < 0.0001); (ii) COPERNICUS (n = 2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P = 0.0014) and MERIT-HFs (n = 795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P = 0.0086); (iii) SENIORS-SHF (n = 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n = 985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P = 0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. CONCLUSION:The efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated.

背景与目标： 目的：四项重要的心力衰竭（HF）关键性β受体阻滞剂试验的纳入标准不同，如果不进行患者分层，则很难进行比较。这项研究的目的是比较类似患者中比索洛尔，美托洛尔控释/缓释（CR / XL），卡维地洛和奈比洛尔对（i）总死亡率，（ii）全因死亡率或住院治疗的影响心血管原因（首次事件发生的时间），（iii）因心力衰竭导致的全因死亡率或住院以及（iv）耐受性（定义为中止随机治疗）。
方法：我们比较了MERIT-HF中的分层亚组与CIBIS-II [纽约心脏协会（NYHA）III / IV级和射血分数（EF）≤35％]和COPERNICUS（NYHA III / IV和EF）的患者<25％）和SENIORS-SHF收缩期HF患者（年龄≥70岁且EF≤35％）。
结果：安慰剂和β受体阻滞剂组的年死亡率为：（i）CIBIS-II（n = 2647），13.2％vs. 8.8％（相对危险度降低34％，95％CI：19-46，P <0.0001）和MERIT-HFs（n = 2002），分别为14.8％和8.6％（相对危险度降低42％，95％CI：24-56，P <0.0001）； （ii）哥白尼（n = 2289），19.7％vs. 12.8％（相对危险度降低35％，95％CI：19-48，P = 0.0014）和MERIT-HFs（n = 795），19.1％vs. 11.7 ％（相对风险降低39％； 95％CI：11-58，P = 0.0086）； （iii）SENIORS-SHF（n = 1359），分别为11.3％和9.7％（相对危险度降低16％，NS）和MERIT-HFs（n = 985），分别为14.8％和10.1％（相对危险度降低32％， 95％CI：2-53，P = 0.038）。对其他评估结果的影响相似。分析表明，在哥白尼和MERIT-HFs亚组中，与安慰剂相比，对β-受体阻滞剂的随机治疗停药更少。
结论：比索洛尔，卡维地洛和美托洛尔CR / XL的疗效和耐受性与收缩期HF患者相似，而与NYHA分级或射血分数无关。奈必洛尔疗效较差，耐受性较差。

BACKGROUND & AIMS: AIMS:The associations between potassium level and outcomes, the effect of sacubitril-valsartan on potassium level, and whether potassium level modified the effect of sacubitril-valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM-HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non-cardiovascular death and heart failure hospitalization, were examined. METHODS AND RESULTS:A total of 8399 patients were randomized to either enalapril or sacubitril-valsartan. Potassium level at randomization and follow-up was examined as a continuous and categorical variable (≤3.5, 3.6-4.0, 4.1-4.9, 5.0-5.4 and ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+  ≥5.5 mmol/L and hypokalaemia as K+  ≤3.5 mmol/L. Compared with potassium 4.1-4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84-3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10-1.83) were associated with a higher risk for cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non-cardiovascular death and heart failure hospitalization. Sacubitril-valsartan had no effect on potassium overall. The benefit of sacubitril-valsartan over enalapril was consistent across the range of baseline potassium levels. CONCLUSIONS:Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

背景与目标： 目的：在PARADIGM-HF中研究了钾水平与预后，沙必比尔-缬沙坦对钾水平的影响以及钾水平是否改变心衰和射血分数降低的患者中沙必比尔-缬沙坦的影响之间的关系。检查了几种结局，包括心血管死亡，猝死，泵衰竭死亡，非心血管死亡和心力衰竭住院。
方法和结果：总共8399例患者被随机分为依那普利或沙比特利-缬沙坦治疗。在各种统计模型中，随机和随访时的钾水平作为连续的分类变量（≤3.5、3.6-4.0、4.1-4.9、5.0-5.4和≥5.5mmol / L）进行检查。高钾血症定义为K≥5.5mmol / L，低钾血症定义为K≤3.5mmol / L。低钾血症[危险比（HR）2.40，95％置信区间（CI）1.84-3.14]和高钾血症（HR 1.42，95％CI 1.10-1.83）均与4.1-4.9 mmol / L钾相比对于心血管死亡。但是，钾异常与猝死和泵衰竭死亡以及非心血管死亡和心力衰竭住院相似。屈比特尔-缬沙坦对钾总体没有影响。在基线钾水平范围内，沙库比曲伐-缬沙坦优于依那普利的益处是一致的。
结论：尽管较高和较低的钾水平都是心血管死亡的独立预测因子，但钾异常可能主要是死亡风险的标志物而不是介质。