Sympathetic nervous system activation and heart failure:Current state of evidence and the pathophysiology in the light of novel biomarkers

Heart failure(HF)is a complex clinical syndrome characterized by the activation of at least several neurohumoral pathways that have a common role in maintaining cardiac output and adequate perfusion pressure of target organs and tissues.The sympathetic nervous system(SNS)is upregulated in HF as evident in dysfunctional baroreceptor and chemoreceptor reflexes,circulating and neuronal catecholamine spillover,attenuated parasympathetic response,and augmented sympathetic outflow to the heart,kidneys and skeletal muscles.When these sympathoexcitatory effects on the cardiovascular system are sustained chronically they initiate the vicious circle of HF progression and become associated with cardiomyocyte apoptosis,maladaptive ventricular and vascular remodeling,arrhythmogenesis,and poor prognosis in patients with HF.These detrimental effects of SNS activity on outcomes in HF warrant adequate diagnostic and treatment modalities.Therefore,this review summarizes basic physiological concepts about the interaction of SNS with the cardiovascular system and highlights key pathophysiological mechanisms of SNS derangement in HF.Finally,special emphasis in this review is placed on the integrative and up-to-date overview of diagnostic modalities such as SNS imaging methods and novel laboratory biomarkers that could aid in the assessment of the degree of SNS activation and provide reliable prognostic information among patients with HF.

Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure

BACKGROUND Chronic heart failure(CHF)is a complex syndrome characterized by a progressive reduction of the left ventricular(LV)contractility,low exercise tolerance,and increased mortality and morbidity.Diastolic dysfunction(DD)of the LV,is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases.Also,it is well estimated that exercise training induces several beneficial effects on patients with CHF.AIM To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction(EF)in patients with CHF.METHODS Thirty-two stable patients with CHF(age:56±10 years,EF:32%±8%,88%men)participated in an exercise rehabilitation program.They were randomly assigned to aerobic exercise(AER)or combined aerobic and strength training(COM),based on age and peak oxygen uptake,as stratified randomization criteria.Before and after the program,they underwent a symptom-limited maximal cardiopulmonary exercise testing(CPET)and serial echocardiography evaluation to evaluate peak oxygen uptake(VO2peak),peak workload(Wpeak),DD grade,right ventricular systolic pressure(RVSP),and EF.RESULTS The whole cohort improved VO2peak,and Wpeak,as well as DD grade(P<0.05).Overall,9 patients(28.1%)improved DD grade,while 23(71.9%)remained at the same DD grade;this was a significant difference,considering DD grade at baseline(P<0.05).In addition,the whole cohort improved RVSP and EF(P<0.05).Not any between-group differences were observed in the variables assessed(P>0.05).CONCLUSION Exercise rehabilitation improves indices of diastolic and systolic dysfunction.Exercise protocol was not observed to affect outcomes.These results need to be further investigated in larger samples.

Cognitive impairment in heart failure patients

在心失败(HF ) 的认知损坏包含因此为单身的病人防碍能力到自顾的不同领域，修改症状和健康行为并且应付治疗政体。许多服、功能的变化在大脑成像被检测，包含灰、白的物质的区域派了到认知。尽管各种各样的仪器是可得到的探索认知，没有一致在在 HF 人口要过去常的更好的工具上被获得。在服的血流动的减小，减少的心脏的输出，血压层次的脑血管的反应和修正的改变是涉及认知赤字的 etiopathogenetic 机制的主要特征。几个心脏的变量，实验室参数，人口统计、临床的元素与认知为他们的可能的关系被学习并且应该适当地被评估在缺陷的增加的风险定义病人。现在的评论收集指出保证信息并且讨论研究开发的可能的区域的可得到的数据。

Differences in the predictive value of red cell distribution width for the mortality of patients with heart failure due to various heart diseases

BackgroundIncreased 红血房间分发宽度(RDW ) 与心失败(HF ) 在病人与不利结果被联系。学习是回顾地由于不同 causes.MethodsWe 在病人在 RDW 的预兆的价值把差别与 HF 作比较的这的目的在 Fuwai 医院(中国北京) 从 2009 年 10 月调查了 1,021 个 HF 病人到 2011 年 12 月。在这些病人的 HF 被三疾病引起；冠的心疾病(CHD ) ，扩大心肌症(DCM ) 和瓣膜的心疾病(VHD ) 。病人们为 21 &#x000b1 是跟随起来的；9 months.ResultsThe RDW，死亡和幸存持续时间在三个组之中是显著地不同的。Kaplan-Meier 分析证明累积幸存在病人与增加的 RDW 显著地减少了， HF 由 CHD 和 DCM 引起了，然而并非在那些，与 HF，病人们由 VHD 引起了。在一个 multivariable 模型， RDW 与 CHD 为 HF 病人的死亡作为一个独立预言者被识别(P &#x0003c；0.001， HR 1.315， 95% CI 1.122-1.543 ) 。有更高的 N 终端支持大脑的 natriuretic 肽(NT-proBNP ) 和更高的 RDW 的组比中部由于 DCM.ConclusionsRDW 与 HF 由于 CHD 与 HF 在病人，然而并非在病人有最低累积幸存为有 HF 的病人的预示的指示物被 CHD 和 DCM 引起；因此， RDW 补充说到在 CHD 的 NT-proBNP 的重要信息引起了 HF 病人。

Assessing inflammation in Chinese subjects with subtypes of heart failure: an observational study of the Chinese PLA Hospital Heart Failure Registry

Background Inflammation is an important element of the pathophysiological process of heart failure (HF) and is correlated with subtypes of HF. The association between multiple biomarkers of inflammation and HF subtypes in Chinese subjects remains unclear. This study aimed to compare the differences in inflammation biomarkers among Chinese patients with different subtypes of HF who have been identified to date. Methods We included 413 consecutive patients with HF,including 262 with preserved ejection fraction (HFpEF),55 with middle-ranged ejection fraction (HFmrEF) and 96 with reduced ejection fraction (HFrEF). Ten inflammation biomarkers were analyzed and compared according to the HF subtypes. One hundred contemporary non-HF subjects were also recruited as the control group. Moreover,the correlations between the inflammatory biomarkers and left ventricular ejection fraction of the HF subtypes were assessed. Results The mean age of the HF patients was 65.0 ± 12.0 years,65.8% were male. Distinct subtypes of HF demonstrated different inflammation biomarker panels. IL-6,PTX-3,ANGPTL-4 and TNF-α were correlated with HFrEF;IL-1β and PTX-3 were correlated with HFmrEF;and IL-1β and IL-6 were correlated with HFpEF. The multivariable logistic regression showed that IL-1β[relative ratio (RR)= 1.08,95% CI: 1.02–1.15,P = 0.010],IL-6 (RR = 1.03,95% CI: 1.01–1.06,P = 0.016),PTX-3 (RR = 1.31,95% CI: 1.11–1.55,P = 0.001),and ANGPTL-4 (RR = 1.05,95% CI: 1.02–1.07,P < 0.001) were independently associated with HF,while IL-6 (RR = 1.03,95% CI: 1.01–1.04,P = 0.019),PTX-3 (RR = 1.23,95% CI: 1.06–1.43,P = 0.007),and ANGPTL-4 (RR = 1.03,95% CI: 1.01–1.06,P = 0.005) were independently associated with the HF subtype. Conclusions Diverse inflammation biomarkers have multifaceted presentations according to the subtype of HF,which may illustrate the diverse mechanisms of inflammation in Chinese HF patients. IL-6,PTX-3,and ANGPTL-4 were independent inflammation factors associated with HFrEF and HF.

Repeated measurement of growth-differentiation factor-15in Chinese Han patients with post-myocardial infarction chronic heart failure

Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with CI-IF in Chinese Han population.This study sought to identify the clinical value of repeated measurement of GDF-15in Chinese Han patients with post-myocardial infarction CHF. Methods In total,232consecutive Chinese Hart patients with post-myocardial infarction CHF were enrolled prospectively from January 2014to June 2016.The plasma concentration of GDF-15was determined on admission and over 12months.Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE)included all-cause death,myocardial infarction and first heart failure (HF)re-hospitalization.Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored.Results The median baseline GDF-15level was 2025ng/L.Baseline GDF-15was moderately associated with baseline N-terminal pro-B type nalriuretic peptide (NT-proBNP)(coefficient 0.561,P <0.001).During a median follow-up of 20months,there were 53deaths and 100MACE.GDF-I5remained an independent predictor of all-cause death (adjusted hazard ratio 1.826per 1Ln U,95%CI: 1.037-8.360;P =0.037)and MACE (adjusted hazard ratio 2.243per I Ln U,95%CI:1.181-1.775;P <0.001)adjusted for established risk factors.Repeated measurement of GDF-15was performed in 173survivals over 12months.Increase of GDF-15over 12months was associ- ated with dilatation of left ventricle and acted as an independent predictor of subsequent all-canse death (adjusted HR =3.164,95%CI: 1.245~.041;P =0.015).In the joint model,GDF-15was also shown to be a risk factor for all-cause death (HR =2.749,95%CI: 1.667-3.831;P <0.001)and MACE (FIR =2.434,95%CI:1.425-3.443;P <0.001).Conclusions Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CI-IF post-myocardial infarction.GDF-15may influence the post-myocardial infarction CI-IF through the path physiological pathway of myocardial remodeling.

Different prognostic association of systolic blood pressure at different time points with postdischarge events in patients hospitalized for decompensated heart failure

Background The association of systolic blood pressure(SBP) with mortality in heart failure(HF) patients is paradoxical, and the time points of baseline SBP are also different across prior studies. We hypothesized that the levels of SBP at admission and at discharge had different associations with postdischarge events. Methods The study population included patients hospitalized for decompensated HF in the Heart Failure Center of Fuwai Hospital from January 1, 2009 to December 31, 2014. The primary outcome was a composite of cardiovascular(CV) death and heart transplantation. Multivariate Cox proportional-hazards and restricted cubic spline analyses were used to assess the relationships between SBP at different time points and outcomes. Results In total, 2005 patients were included with a median follow-up of 48.4 months. The median age was 59 years, and 69.9% were male. Multivariate Cox analyses showed that compared with SBP < 105 mm Hg, higher SBP at admission was associated with better long-term primary outcome(105–119 mm Hg, HR = 0.764, P = 0.005;120-134 mm Hg, HR = 0.658, P < 0.001;≥ 135 mm Hg, HR = 0.657, P = 0.001). Patients whose discharge SBP was higher than 135 mm Hg had a similar primary outcome as those with SBP < 105 mm Hg(HR = 0.969, P = 0.867), and the results remained unchanged even after adjusting for admission SBP(HR = 1.235, P = 0.291). The results of restricted cubic spline analysis indicated similar associations. Conclusions Lower but not higher SBP at admission is associated with more CV deaths/heart transplantations(a reverse J-shaped curve). In contrast, there is a U-shaped association between discharge SBP and CV mortality/heart transplantation.

Highlights of the physical examination in heart failure

Because decompensated heart failure (HF) patients present primarily with symptoms of congestion, the assessment of volume status is of paramount importance. Despite the addition of new technologies that can predict intracardiac filling pressures, the physical exam (PE) remains the most accessible and cost-effective tool available to clinicians. An elevated jugular venous pressure (JVP)useful cutoff is that if the JVP is greater than 3 cm in vertical distance above the sternal angle, the central venous pressure is elevated. In addition to assessment of volume status, the PE in HF can reveal adverse prognostic signs, namely: elevated JVP, presence of third heart sound, elevated heart rate, low systolic BP, and low proportional pulse pressure (＜ 25%). This article will review the evidence for the diagnostic and prognostic utility of common PE findings in HF.

Late-chronic cardiotoxicity and heart failure caused by ibrutinib:a case report and literature review

Richter syndrome (RS) is a rare transformation of relatively low-grade malignant chronic lymphocytic leukemia (CLL) to more aggressive lymphoma. The most common form of RS is transformation to diffuse large B-cell lymphoma (> 95%) and much less frequently (<1%)to Hodgkin lymphoma (HL), plasma blast lymphoma, or other rare lymphomas.

Quality of life in elderly heart failure patients

Quality of life (QOL), as a relevant area of research in the understanding of heart failure (HF) patient outcomes, has been increasingly studied during the last two decades. The purposes of this review article are to (1) describe QOL in older adults with HF, (2)identify and critique research designed to test interventions to improve QOL, (3) identify gaps in the literature, and (4) provide recommendations for future research. Seventeen studies describing QOL in older adults with HF were identified. Elderly HF patient QOL has been reported to be fair to poor and is worse as compared to a healthy control group. Furthermore, there is some evidence that suggests that QOL is better in older adults than younger adults and worse in women (both older and younger) than in men, although these findings are not consistent across studies. Predictors of QOL and its dimensions in older HF patients included demographic, clinical, and psychosocial variables. Sixteen interventional studies were identified that reported QOL as an outcome in older adults. Findings among randomized clinical trials (RCTs) to improve QOL outcomes in elderly HF patients do not allow strong conclusions about the benefits of the interventions. It must be noted, though, that while not all studies reported improvements in QOL (either significant or as a trend),no studies reported deterioration in QOL with randomization to an intervention versus control. These studies were limited by several methodological issues. While there has been some research of QOL in this elderly cohort, it is paramount that we address methodological issues and thereby improve the scientific rigor of our research, continue to explore QOL in elderly HF patients, and design intervention trials for elders at risk for poor QOL.

Prognostic factors in patients hospitalized with acute heart failure syndrome

Each year, there are over one million hospitalizations for acute heart failure syndrome (AHFS) in the United States alone,with a similar number in Western Europe. These patients have very high short-term (2-6 months) mortality and readmission rates, while the healthcare system incurs substantial costs. Until recently, the clinical characteristics, management patterns, and outcomes of these patients have been poorly understood and, in consequence, risk stratification for these patients has not been well defined. Several risk prediction models that can accurately identify high-risk patients have been developed in the last year using data from clinical trials, large registries or administrative databases. Use of multi-variable risk models at the time of hospital admission or discharge offers better risk stratification and should be encouraged, as it allows for appropriate allocation of existing resources and development of clinical trials testing new treatment strategies for patients admitted with AHFS. The emerging observation that the prognosis for the ensuing three to six months may be obtained at presentation for AHFS has major implications for development of future therapies.

Diastolic heart failure in the elderly

Heart failure with preserved left ventricular function is a common problem among elderly patients. Given that diastolic heart failure (DHF) occurs in up to 50% of all heart failure admissions, and that incidence increases with age, knowledge of current recommendations for its diagnosis and treatment are extremely important for the elderly population. Causes of DHF include the aging process itself, hypertension, left ventricular hypertrophy, aortic stenosis, and hypertrophic obstructive cardiomyopathy. The patient with DHF may present with signs and symptoms similar to those observed in systolic heart failure. Treatment goals for the patient with DHF include achieving normal volume status, improving relaxation of the left ventricle, regression of hypertrophy if possible, and management of any co-morbidities that may aggravate the clinical status of patients with DHF. Hopefully, in the future, further data from randomized clinical trials will allow a more defined approach to care in these patients.

Myocardial disease,anemia and heart failure

Abstract Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, very poor quality of life, end stage renal failure, or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these patients is the fact that they are often anemic.The anemia is due mainly to renal failure but also to the inhibitory effects of cytokines on the bone marrow. Anemia itself may further worsen the cardiac function and make the patients resistant to standard CHF therapies. Indeed anemia has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, higher doses of diuretics,worsening of renal function and reduced quality of life. In both controlled and uncontrolled studies the correction of the anemia with erythropoietin (EPO) and oral or Ⅳ iron is associated with improvement in all these parameters. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia. Anemia may also play a role in the worsening of coronary heart disease even without CHF.

Secondary lymphoma develops in the setting of heart failure when treating breast cancer: A case report

BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.

Study the Effect of Spironolactone in Airway Resistance with Impulse Oscillometry in Patients with Congestive Heart Failure

Background: CHF (Congestive Heart Failure) is one of the most important causes of mortality and morbidity in the world. Diuretics such as spironolactone can decrease pulmonary congestion and reduce the amount of fibrosis in CHF patients. The goal was to assess whether spironolactone can decrease air way resistance and can we follow up the effect of diuretic therapy in patients of heart failure quantitatively by means of impulse oscillometry. Methods: It was clinical trial which performed in Ahvaz teaching hospital. 24 patients with congestive heart failure (CHF) which was classified as functional class II-IV and had EF Result: The age of patient was 61 ± 10 and the age of control was 57 ± 7 years old. The data of oscillometry before and after spironolactone were X5 (&minus;0.14 ± 0.05 vs &minus;0.14 ± 0.05, P: 0.93), R5 (0.39 ± 0.21 vs 0.39 ± 0.15, P: 0.35), X20 (&minus;0.04 ± 0.06 vs &minus;0.06 ± 0.06, P: 0.37), R20 (0.04 ± 0.03 vs 0.06 ± 0.06, P: 0.37), Zrs (0.39 ± 0.21 vs 0.39 ± 0.15, P: 0.35). Conclusion: There was a trend toward reduction of peripheral airway resistances in CHF patients than controls with use of 1 month of spironolactone. Although there was not significant change in the number of X5, R5, X20, R20 occurred the trend toward reduction of number triggers the point that oscillometry can be used for quantitative follow up of CHF patients.

Acute heart failure in the elderly:setting related differences in clinical features and management

BACKGROUND Administrative data show that acute heart failure(HF)patients are older than those enrolled in clinical registries and frequently admitted to non-cardiological settings of care.The purpose of this study was to describe clinical characteristics of old patients hospitalised for acute HF in Cardiology,Internal Medicine or Geriatrics wards.METHODS Data came from ATHENA(AcuTe Heart failurE in advaNced Age)registry which included elderly patients(≥65 years)admitted to the above mentioned settings of care from December 1,2014 to December 1,2015.RESULTS We enrolled 396 patients,15.4%assigned to Cardiology,69.7%to Internal Medicine,and 14.9%to a Geriatrics ward.Mean age was 83.5±7.6 years(51.8%of patients≥85 years)and was higher in patients admitted to Geriatrics(P<0.001);more than half were females.Medical treatments did not differ significantly among settings of care(in a context of a low prescription rate of renin-angiotensin-aldosterone system inhibitors)whereas significant differences were observed in comorbidity patterns and management guidelines recommendation adherence for decongestion evaluation with comparison of weight and N-terminal pro-B-type natriuretic peptide levels on admission and at discharge(both P=0.035 and P<0.001),echocardiographic evaluation(P<0.001)and follow-up visits planning(P<0.001),all higher in Cardiology.Mean in-hospital length of stay was 9±5.9 days,significantly higher in Geriatrics(13.7±6.5 days)and Cardiology(9.9±6.7 days)compared to Internal Medicine(8±5.2 days),P<0.001.In-hospital mortality was 9.3%,resulting higher in Geriatrics(18.6%)and Cardiology(16.4%)than Internal Medicine(5.8%),P=0.001.CONCLUSIONS In elderly patients hospitalised for acute HF,clinical characteristics and management differ significantly according to the setting of admission.

Telemonitoring and hemodynamic monitoring to reduce hospitalization rates in heart failure： a systematic review and meta-analysis of randomized controlled trials and real-world studies

BackgroundHeart 失败是导致重复住院的一个重要问题。Telemonitoring 并且血液动力学的监视在减少住院率表明了成功，然而并非所有研究报导了重要效果。系统的评论和元分析是在在心 failure.Methods 与 ResultsPubMed 和 Cochrane 图书馆减少住院检验 telemonitoring 和无线血液动力学的监视设备的有效性的这的目的被寻找直到 1 为调查了 telemonitoring 或在住院上的血液动力学的监视的效果的文章的 st 2017年5月评价在心失败。在 31,501 个病人(吝啬的年龄：68 #

Relationship of the plasma urotensin Ⅱ with proadrenomedullin N-terminal 20 peptide in patients with congestive heart failure

Objective: To understand the role of urotensin Ⅱ(UⅡ) and proadrenomedullin N-terminal 20 peptide (PAMP), a fragment of proadrenomedullin (proADM) possessing biological activity, in the pathophysiological process of congestive heart failure (CHF) by observing the variation of their plasma levels and exploring their interrelations. Methods: Plasma UⅡ and PAMP levels were measured by radioimmunoassay in 52 patients with CHF and 14 healthy subjects. Left ventricular ejection fraction (LVEF) and the ratio of E/A were determined by echocardiography. Results: The plasma UⅡ level was significantly lower in patients with CHF than the healthy subjects (1.5±1.0 pg/ml vs 4.3±1.2 pg/ml, P<0.05), while plasma PAMP level was significantly higher in the former group (30.6±5.8 pg/ml vs 21.0±6.6 pg/ml P<0.05). The levels of UⅡ and PAMP were parallel with the severity of CHF, and significant correlation of plasma levels of UⅡ with LVEF (r=0.530, P=0.000) and the ratio of E/A (r=0.618, P=0.000) was noted. LVEF and ratio of E/A were found to be inversely correlated with plasma PAMP levels in the patients (r=-0.568, P=0.000; r=-0.350, P=0.004). Also found was the significant correlation between plasma UⅡ and PAMP levels (r=-0.528, P=0.000). The treatment of the patients resulted in increased plasma UⅡ levels and lowered PAMP levels. Conclusion: The variations of plasma levels of UⅡ and PAMP are parallel with the severity of CHF, suggesting their cooperative actions in the pathophysiology of CHF.