急性心力衰竭的流行现状和诊治进展

急性心力衰竭是年龄≥65岁住院患者主要的死亡原因,其早期住院死亡率及再入院率均高,住院期间及出院后涉及预后的影响因素众多。B型利钠肽和肌钙蛋白是独立的急性心力衰竭预后指标,有助于急性心力衰竭患者的危险评估。目前治疗急性心力衰竭的传统药物由于作用单一,应用各有局限性。新的药物奈西立肽、重组人心钠肽和钙增敏剂(左西孟旦)对心力衰竭的治疗已显示出良好的效果,是有望突破急性心力衰竭治疗瓶颈的药物。     

B型脑钠肽与不同病因心力衰竭的研究进展

B型脑钠肽(BNP)是心力衰竭的重要标记物,在不同病因导致的心力衰竭中,其浓度有所不同,但对于心力衰竭的预后评估和治疗起到指导作用.BNP的基因重组药物对于急性心力衰竭,特别是急性冠脉综合征导致的心力衰竭有很好的疗效,但对于慢性心力衰竭的长期预后影响需进一步验证.     

心钠肽在急性心力衰竭治疗中的研究进展

治疗急性心力衰竭的传统药物,如:利尿剂、血管扩张剂、肾上腺素能受体激动剂、磷酸二酯酶抑制剂等不仅作用单一,而且各有其局限性。血浆心钠肽具有扩血管、利尿、拮抗神经内分泌激素的多种作用。基因重组人心钠肽与内源性心钠肽具有相同的生物学作用,对急性心力衰竭的治疗已经显示出良好的效果。     

脑钠肽在心力衰竭中的应用进展

心力衰竭是很多心血管疾病的最终转归,脑钠肽作为心力衰竭的诊断、鉴别诊断、预后和指导治疗的新指标,以及作为一类治疗心力衰竭的新型药物都有其重要的价值.在国内外颇受关注.脑钠肽的作用机制也在不断探索中.     

和肽素在慢性心力衰竭急性发作期治疗中的变化与预后的关系

目的 研究和肽素在慢性心力衰竭急性发作期治疗前后的变化,及其对病情评估、预后判断的价值.方法 选择慢性心力衰竭急性发作患者80例为心力衰竭组,健康对照组30例.心力衰竭组分别于入院即刻、治疗10 d后测定血浆和肽素、氮末端脑钠肽前体（NT-proBNP）水平,入院后24h内行心脏超声检查,测量左心室舒张末期内径（LVIDd）和左心室射血分数（LVEF）;出院后3个月时随访其是否发生心血管事件（包括心力衰竭、恶性心律失常、死亡等）.结果 心力衰竭组入院即刻和肽素、NT-proBNP水平均高于对照组（均为P＜0.01）;心力衰竭组治疗10 d后和肽素、NT-proBNP水平较入院时明显下降（均为P＜0.01）;出院后3个月时间内,与未发生心血管事件的患者相比,发生心血管事件患者的和肽素、NT-proBNP水平在治疗前后均较高（均为P＜0.01）;用全模型多元Logistic回归分析,入院时和肽素水平为慢性心力衰竭患者独立预后指标（P＜0.01）.结论 慢性心力衰竭急性发作期和肽素、NT-proBNP水平升高,治疗后其水平明显下降;监测和肽素浓度对心力衰竭患者的危险分层及预后判断有重要意义.     

利钠肽系统的调节及其在心力衰竭时的变化

利钠肽是心血管系统分泌的肽类,这一系统通过利尿利钠调节体液平衡,舒张血管,降低心脏后负荷;同时通过旁分泌／自分泌方式抑制心肌细胞肥大,减缓心室重构。利钠肽系统的激活是心力衰竭时心血管系统重要的代偿机制之一。重组人B型利钠肽（rhBNP）已用于治疗急性失代偿性心力衰竭,并能够迅速改善心力衰竭患者的临床症状。但是,rhBNP在临床使用过程中,除了药物的安全性曾引起较大的疑虑外,肾脏、血管等器官对利钠肽存在低反应性;而且在大规模的临床试验中,rhBNP也未能增加心力衰竭患者的生存率。因此,对利钠肽系统在心力衰竭时的调节研究,有助于对疾病的认识。     

新型血管扩张剂治疗急性心力衰竭研究进展

每年全球有数百万患者因急性心力衰竭发作入院,如何改善急性心力衰竭患者的临床预后是一项巨大的挑战。在急性心力衰竭患者中,血管扩张剂是继利尿剂之后第二常用的药物。当前仍缺乏足够证据证明传统药物治疗在改善急性心力衰竭患者的临床预后上有明显获益。近些年,在药物治疗急性心力衰竭的研究中研发了一些新型血管扩张剂,包括可溶性鸟苷酸环化酶调节剂、新型硝酰基前体药物、利钠肽、松弛素及血管紧张素受体偏配体,旨在改善急性心力衰竭患者住院期间及出院后的临床结局。     

重组人脑利钠肽治疗急性心梗后失代偿性心力衰竭的疗效观察

目的本文研究重组人脑利钠肽应用于急性心梗后失代偿性心力衰竭的疗效。方法选取我院2013年03月~2015年03月收治的急性心梗后失代偿性心力衰竭患者120例作为研究对象,将其平均划分为观察组(n=60例)与对照组(n=60例),分别予以重组人脑利钠肽、多巴酚丁胺治疗。对比2组患者治疗后的血脑钠肽水平(BNP)、左室射血分数(EF)。结果观察组经重组人脑利钠肽治疗后的血脑钠肽水平明显低于对照组(P0.05);观察组的左室射血分数则高于对照组(P0.05)。结论将重组人脑利钠肽药物应用于急性心梗后失代偿性心力衰竭患者中可降低血脑钠肽水平,改善患者的心功能。     

利钠肽系统的调节及其在心力衰竭时的变化

利钠肽是心血管系统分泌的肽类,这一系统通过利尿利钠调节体液平衡,舒张血管,降低心脏后负荷;同时通过旁分泌/自分泌方式抑制心肌细胞肥大,减缓心室重构.利钠肽系统的激活是心力衰竭时心血管系统重要的代偿机制之一.重组人B型利钠肽(rhBNP)已用于治疗急性失代偿性心力衰竭,并能够迅速改善心力衰竭患者的临床症状.但是,rhBNP在临床使用过程中,除了药物的安全性曾引起较大的疑虑外,肾脏、血管等器官对利钠肽存在低反应性;而且在大规模的临床试验中,rhBNP也未能增加心力衰竭患者的生存率.因此,对利钠肽系统在心力衰竭时的调节研究,有助于对疾病的认识.     

脑尿钠肽在充血性心力衰竭以外的一些疾病中的研究进展

脑尿钠肽被公认为是心力衰竭的重要标志物,在心力衰竭的诊断、治疗和预后评估中发挥着重要作用。但随着对脑尿钠肽研究的深入,人们发现脑尿钠肽在其它一些疾病中（如急性冠状动脉综合征、心律失常、肺部疾病、肾脏疾病等）也有不同程度的升高,并有其相应的变化规律和临床意义。在这里我们就脑尿钠肽在充血性心力衰竭外的这些疾病中的研究进展作简单综述,以更全面理解脑尿钠肽的变化规律,更好使用脑尿钠肽指导临床治疗。     

The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT-proBNP and cardiac troponin-T

AIMS: Brain natriuretic peptide (BNP), NT-proBNP and troponins are useful for the assessment of patients with heart failure. Few data exist about their serial changes and their prognostic value in patients with acute heart failure (AHF). METHODS AND RESULTS: NT-proBNP and troponin-T plasma levels were measured at baseline, after 6, 12, 24, 48 h and at discharge in 116 consecutive patients with AHF and no evidence of acute coronary syndrome. NT-proBNP levels were 4421 pg/mL at baseline, declined after 24 h and reached their nadir at 48 h (2703 pg/mL). Troponin-T was detectable in 48% of patients. During a median follow-up of 184 days, 52 patients died or had a non-fatal cardiovascular hospitalisation. At a multivariable analysis including clinical and echo-Doppler variables, NT-proBNP plasma levels at discharge, detectable troponin-T plasma levels, and NYHA class at discharge were the only independent prognostic factors. CONCLUSION: In patients with AHF, NT-proBNP levels decline 24 h after the initiation of intravenous therapy and troponin-T is detectable in 48% of cases. NT-proBNP levels at discharge, detectable troponin-T levels, NYHA class and serum sodium have independent prognostic value.     

Impact of kidney dysfunction on plasma and urinary N-terminal pro-B-type natriuretic peptide in patients with acute heart failure

The precise mechanism explaining the increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among patients with concomitant acute heart failure (AHF) and kidney dysfunction is not fully understood. The aim of this study was to assess the impact of kidney dysfunction on simultaneous measures of plasma and urinary NT-proBNP in an unselected cohort of patients with AHF. One hundred thirty-eight consecutive hospitalized patients (median age: 74 years; interquartile range: 67-80 years; 54% male) with a diagnosis of AHF were prospectively studied. Blood and urine samples were collected on hospital arrival to determine NT-proBNP concentrations. Both plasma and urinary NT-proBNP concentrations increased with declining estimated glomerular filtration rate (eGFR; P<.001 for both). However, after multivariate adjustment, eGFR was found to be an independent predictor of plasma (but not urinary) NT-proBNP concentration (eGFR: β=-0.19; P=.016). Indeed, plasma NT-proBNP was the main independent determinant of its urinary concentration (β=0.42; P<.001), and the ratio of urine/plasma NT-proBNP was independent of kidney function and similar across the range of eGFR examined (P=.368). In patients with AHF and concomitant kidney dysfunction, the increased circulating NT-proBNP may be mainly related to increased cardiac secretion and not decreased renal clearance.     

Prognostic value of cystatin C in acute heart failure in relation to other markers of renal function and NT-proBNP.

AIMS: Cystatin C, a novel marker of renal function, has been implicated as a prognostic marker in cardiovascular disease. We investigated the prognostic value of cystatin C in acute heart failure (AHF) in comparison to other markers of renal function and NT-proBNP. METHODS AND RESULTS: Patients with cystatin C measurements (n = 480) from a prospective multicentre study on AHF were included. All-cause mortality at 12 months was 25.4%. Cystatin C, creatinine, age, gender, and systolic blood pressure on admission were identified as independent prognostic risk factors. Cystatin C above median (1.30 mg/L) was associated with the highest adjusted hazard ratio, 3.2 (95% CI 2.0-5.3), P < 0.0001. Mortality increased significantly with each tertile of cystatin C. Combining tertiles of NT-proBNP and cystatin C improved risk stratification further. Moreover, in patients with normal plasma creatinine, elevated cystatin C was associated with significantly higher mortality at 12 months: 40.4% vs. 12.6% in patients with both markers within normal range, P < 0.0001. CONCLUSION: Cystatin C is a strong and independent predictor of outcome at 12 months in AHF. Furthermore, cystatin C identifies patients with poor prognosis despite normal plasma creatinine. Cystatin C seems to be a promising risk marker in patients hospitalized for AHF.     

老年糖尿病患者急性心衰时急性肾损伤发生及预后分析

【】　目的　分析老年糖尿病(DM)合并急性心衰(acute heart failure,AHF)患者急性肾损伤(acute kidney injury,AKI)发生情况及短期预后。方法 107例老年糖尿病合并急性心衰患者作为观察组, 老年非糖尿病合并急性心衰患者79例作为对照组,采集两组患者一般情况、病史、尿素氮、肌酐、左室射血分数(LVEF)、血浆NT-proBNP等指标,观察随访两组患者住院期间AKI发生情况,院内死亡情况和住院时间。6个月时随访心血管事件发生率及死亡情况。按院内是否发生AKI进行组内对比,了解亚组间死亡率的差异。结果　观察组患者的AKI发生率、平均住院时间及院内死亡率高于对照组 (P<0.05);观察组患者60天心血管事件发生率高于对照组差异(P<0.05);发生院内AKI的患者死亡率明显升高(P<0.05)。结论　合并糖尿病的老年急性心衰患者AKI发生率高,院内死亡率高,院外心血管事件发生率高,并且发生AKI的患者死亡率更高。     

Risk Stratification With the Use of Serial N-Terminal Pro–B-Type Natriuretic Peptide Measurements During Admission and Early After Discharge in Heart Failure Patients: Post Hoc Analysis of the PRIMA Study

ObjectiveThe aim of this work was to assess the prognostic value of absolute N-terminal-pro–B-type natriuretic peptide (NT-proBNP) concentration in combination with changes during admission because of acute heart failure (AHF) and early after hospital discharge.BackgroundIn AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring.Methods and resultsWe evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. Primary outcome measures were mortality and the combined end point of heart failure (HF) readmission or mortality. In a multivariate Cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at 1 month after discharge were of independent prognostic value for both end points (hazard ratios for HF readmission or mortality: 1.71, 95% confidence interval [CI] 1.13–2.60, Wald 6.4 [P = .011] versus 2.71, 95% CI 1.76–4.17, Wald 20.5 [P < .001] versus 1.81, 95% CI 1.13–2.89, Wald 6.1 [P = .014], respectively.ConclusionsKnowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at 1 month after discharge allows accurate risk stratification.     

Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study

Patients admitted for acute heart failure (AHF) experience high rates of in‐hospital and post‐discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin‐2, a hormone with vasodilatory and end‐organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX‐AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all‐cause and cardiovascular mortality by 37% through day 180. RELAX‐AHF‐2 ( ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX‐AHF‐2 is a multicentre, randomized, double‐blind, placebo‐controlled, event‐driven, phase 3 trial enrolling ～6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild‐to‐moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all‐cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in‐hospital length of stay during index AHF. The results from RELAX‐AHF‐2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF.     

急性心力衰竭患者血清半乳凝素-3的变化及临床意义

目的 :通过检测急性心力衰竭(心衰)患者血清半乳凝素-3(galectin-3,Gal-3)的变化,探讨Gal-3在心衰发病中的作用。方法:选择急性心衰患者120例,其中纽约心脏病协会(NYHA)心功能Ⅱ级30例,Ⅲ级50例,Ⅳ级40例。于治疗前、后检测Gal-3和氨基末端脑钠肽前体(NT-proBNP),超声心动图测左心房内径(LAD)、左心室舒张末期内径(LVEDD)和左心室射血分数(LVEF)。并以健康体检者40名为对照组。结果:NYHAⅡ~Ⅳ级组血Gal-3、NTproBNP水平高于对照组(P<0.05);各亚组之间Gal-3、NT-proBNP水平均有差异(均P40%组(P70 mm组Gal-3水平高于LVEDD<0.05);NT-proBNP在治疗前、后均无差异。治疗前Gal-3、NT-proBNP水平分别与NYHA分级、LAD、LVEDD呈正相关、与LVEF呈负相关(r分别为0.64、0.48、0.67、-0.67,P<0.05或P<0.05)。发生心脏不良事件者Gal-3、NT-proBNP水平更高。结论:急性心衰患者血Gal-3水平与心衰严重程度相关,与左心室的结构和功能相关,提示Gal-3可能参与急性心衰的发病过程。Gal-3和NT-proBNP水平同时异常升高者近期预后差。     

Prognostic value of serum cystatin C and N-terminal pro b-type natriuretic peptide in patients with acute heart failure

BackgroundCystatin C (CysC) is a good prognostic marker in heart failure. However, there is not much information of CysC combined with other biomarkers in acute heart failure (AHF).AimTo assess prognostic value of CysC and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients hospitalized for AHF with no apparent deterioration of renal function.DesignProspective, multicenter, observational study.MethodsCysC and NTpro-BNP were measured in patients consecutively admitted with a diagnosis of AHF. Patients with, NTpro-BNP concentration above 900 pg/mL and serum creatinine below 1.3 mg/dL, were included for statistical analysis. End-point of the study was all-cause mortality during a 12-month follow-up.Results526 patients with AHF and NTpro-BNP concentration above 900 pg/mL were included in the study. From this group, 367 patients (69.8%) had serum creatinine below 1.3 mg/dL. Receiver operating characteristic (ROC) curves were used to determine the best cut-off value for CysC. Patients with a concentration of CsyC above 1.25 mg/dL had a 37.8% mortality rate, vs. 13.6% for those below cut-off (p < 0.001). After Cox proportional hazard model, age, CysC, low total cholesterol and HF with preserved ejection fraction remained significantly associated with all-cause mortality during one-year follow-up.ConclusionsIn AHF and normal or slightly impaired renal function, performance of CysC may be superior to NT-proBNP. Hence, CysC may be the preferred biomarker in the assessment of patients with AHF and slightly impaired renal function.     

Prevalence,Related Factors and Association of Left Bundle Branch Block With Prognosis in Patients With Acute Heart Failure: a Simultaneous Analysis in 3 Independent Cohorts

ObjectivesTo determine the prevalence, characteristics and association with prognosis of left bundle branch block (LBBB) in 3 different cohorts of patients with acute heart failure (AHF).Methods and ResultsWe retrospectively analyzed 12,950 patients with AHF who were included in the EAHFE (Epidemiology Acute Heart Failure Emergency), RICA (National Heart Failure Registry of the Spanish Internal Medicine Society), and BASEL-V (Basics in Acute Shortness of Breath Evaluation of Switzerland) registries. We independently analyzed the relationship between baseline and clinical characteristics and the presence of LBBB and the potential association of LBBB with 1-year all-cause mortality and a 90-day postdischarge combined endpoint (Emergency Department reconsultation, hospitalization or death). The prevalence of LBBB was 13.5% (95% confidence interval: 12.9%–14.0%). In all registries, patients with LBBB more commonly had coronary artery disease and previous episodes of AHF, were taking chronic spironolactone treatment, had lower left ventricular ejection fraction and systolic blood pressure values and higher NT-proBNP levels. There were no differences in risk for patients with LBBB in any cohort, with adjusted hazard ratios (95% confidence interval) for 1-year mortality in EAHFE/RICA/BASEL-V cohorts of 1.02 (0.89–1.17), 1.15 (0.95–1.38) and 1.32 (0.94–1.86), respectively, and for 90-day postdischarge combined endpoint of 1.00 (0.88–1.14), 1.14 (0.92–1.40) and 1.26 (0.84–1.89). These results were consistent in sensitivity analyses.ConclusionsLess than 20% of patients with AHF present LBBB, which is consistently associated with cardiovascular comorbidities, reduced left ventricular ejection fraction and more severe decompensations. Nonetheless, after taking these factors into account, LBBB in patients with AHF is not associated with worse outcomes.     

Clinical benefits of natriuretic peptides and galectin-3 are maintained in old dyspnoeic patients

BackgroundAcute dyspnoea is the leading cause of unscheduled admission of elderly patients. Several biomarkers are used to diagnose acute heart failure (AHF) and assess prognosis of dyspnoeic patients, but their value in elderly patients is unclear. Objective: To compare diagnostic and prognostic performances of conventional and novel cardiovascular biomarkers in 2 age groups: young (<75 years old) vs. old (≥75 years old) dyspnoeic patients.DesignProspective observational registry.SettingEmergency department (ED).SubjectsAcutely dyspnoeic adult patients.MethodsBlood samples were collected at ED admission. The diagnostic value of 4 natriuretic peptides (BNP, proBNP, NT-proBNP, MR-proANP) for AHF was tested. We also assessed the prognostic value of same natriuretic peptides and of 3 novel cardiovascular biomarkers (galectin-3, sST2 and proenkephalin), using 1-year all-cause mortality as end-point. Diagnostic or prognostic performances are expressed as area under the receiveroperating characteristic curve (AUC) with 95% confidence interval.ResultsTwo hundred one acutely dyspnoeic patients were studied. AHF was the cause of dyspnoea in 57% of old and 44% of young patients, respectively. All 4 natriuretic peptides performed well in diagnosing AHF in both age groups (all AUC > 0.7). BNP showed the best diagnostic performance in both old (AUC: 0.98 [0.97–1.00]) and young (AUC 0.98 [0.95–1.00]) patients. Galectin-3 showed the best prognostic performance in both old (AUC 0.74 [0.62–0.87]) and young patients (AUC 0.75 [0.56–0.94]).ConclusionsBNP and galectin-3 show good clinical benefits in both oldand young acutely dyspnoeic patients.