Cardiac biomarkers in heart failure

Background

Heart failure is a syndrome characterized by the inability of the heart to meet the body's circulatory demands. Heart failure is a growing health issue worldwide and the prevalence of heart failure is expected to rise as populations age. Therapies and interventions for a variety of cardiac conditions continue to advance and biomarkers will play an increasing role in patient management.

Methods

This is a review of the clinical research in blood based biomarkers for diagnosis, prognosis and therapeutic guidance of heart failure. The focus of this review is biomarkers that are currently available for clinical measurement, and their current and potential for applications for managing heart failure patients.

Results

The various biologic pathways and physiologic processes of heart failure biomarkers represent a host of different including inflammation, remodeling, strain, neurohormonal activation, metabolism and cardiac myocyte injury. The clinical characteristics and applications of each heart failure biomarker are discussed.

Conclusion

As populations age and effective treatments and interventions for coronary artery disease improve, heart failure will increase in incidence and prevalence. Blood biomarkers will play an increasing role in the early diagnosis, therapeutic monitoring and management of heart failure patients in the future.     

Novel biomarkers for heart failure

Heart failure (HF) has proven to be a major burden on the health system. The continuing prevalence of the condition and its rising associated costs and care, has amplified the need for earlier diagnosis, better risk stratification and cost-effective treatment to cut rates of hospitalization. Biomarkers seem poised to undertake such tasks, with biomarker management of patients with HF quickly evolving over the past several years. Biomarker guided diagnosis and treatment has become vital, especially during the acute setting in which the majority of patients with HF, were initially present. An adequate assessment of risk requires a multi-marker approach to a given HF patient. Established markers including brain natriuretic peptide and NT-proBNP are a significant clinical aid to physicians, though their utility is limited. In the past few years, momentous effort has been put into the discovery of new biomarkers. These endeavors have led to the emergence of several capable and promising biomarkers for HF management including troponins, mid-regional pro-adrenomedullin, GDF-15, C-reactive protein, Galectin-3, IL-6, ST-2, neutrophil gelatinase-associated lipocalin, copeptin and procalcitonin. This review will offer an insight into the novel biomarkers considered as the cutting-edge in the diagnosis and management of HF.     

心力衰竭炎症标志物的研究进展

心力衰竭(heart failure,HF)是各种心脏疾病的急性加重或终末期表现,HF的病理生理机制一直都是心血管领域研究的重点内容。近年来对HF炎症标志物的研究较多,如半乳糖凝集素-3(Gal-3)、可溶性肿瘤发生抑制蛋白2(s ST2)、生长分化因子-15(GDF-15)、肿瘤坏死因子-α(TNF-α)、性别决定域Y盒9(Sox9)、高迁移率蛋白-1(HMGB1)以及其他标志物等,与HF的发生中心肌肥厚、心肌纤维化等病理生理过程有密切的联系。     

Using biomarkers to guide heart failure management

Introduction: Biomarkers have revolutionized the diagnosis of heart failure (HF), but it remains unclear how to use biomarkers to guide management of HF.

Areas covered: An exhaustive literature search on using biomarkers to guide HF management was performed. HF guidelines were carefully scrutinized for references pertaining to this topic, and Medline was employed to identify further references. This review focused on natriuretic peptides, troponin, and ST2 as biomarkers used to guide HF management. Most trials have examined secondary prevention of chronic HF patients, and data on primary prevention of HF and therapy of acute HF are emerging.

Expert commentary: While the current data on using biomarkers to guide HF management remain mixed, more research is necessary to better understand how to utilize biomarkers to improve HF management.     

Strategies for developing biomarkers of heart failure

BACKGROUND: Heart failure (HF) is a devastating disease with increasing prevalence in elderly populations. One-half of all patients die within 5 years of diagnosis. The annual cost of treating patients with HF in the US is more than $20 billion, which is estimated to be greater than that of myocardial infarction and all cancers combined. Given the complex pathophysiology and varied manifestations of HF, interest has intensified in developing biological markers to predict susceptibility and aid in the early diagnosis and management of this disease. METHODS: We searched Medline via Ovid for studies published during the period 1966-2003 regarding various biomarkers suggested for HF. Our review focused on developing strategies for discovering and using new biomarkers, particularly those potentially linked to pathophysiologic mechanisms. We also point out strategic advantages, limitations, and methods available for measuring each of the currently proposed markers. RESULTS: Biomarkers reviewed include those released from the heart during normal homeostasis (natriuretic peptides), those produced elsewhere that act on the heart (endogenous cardiotonic steroids and other hormones), and those released in response to tissue damage (inflammatory cytokines). The concept of using a combination of multiple markers based on diagnosis, prognosis, and acute vs chronic disease is also discussed. In view of recent advances in our understanding of molecular biochemical derangements observed during cardiac failure, we consider the concept of myocardial remodeling and the heart as part of an endocrine system as strategies. CONCLUSION: Strategically, biomarkers linked to mechanisms involved in the etiology of HF, such as dysregulation of ion transport, seem best suited for serving as early biological markers to predict and diagnose disease, select therapy, or assess progression.     

The current status of heart failure diagnostic biomarkers

Heart failure (HF) affects approximately 23 million individuals worldwide and this number is increasing, due to an aging and growing population. Early detection of HF is crucial in the management of this debilitating disease. Current diagnostic methods for HF rely heavily on clinical imaging techniques and blood analysis, which makes them less than ideal for population-based screening purposes. Studies focusing on developing novel biomarkers for HF have utilized various techniques and biological fluids, including urine and saliva. Promising results from these studies imply that these body fluids can be used in evaluating the clinical manifestation of HF and will one day be integrated into a clinical workflow and facilitate HF management.     

心力衰竭生物标志物中国专家共识

心力衰竭(以下简称"心衰")的发病率正在随着人口老龄化不断增加,对其早期诊断和优化治疗非常重要。心衰生物标志物可以辅助心衰的预测、早期诊断、预后评估和指导治疗,对心衰的防治非常重要。钠尿肽是发现最早和应用最广的心衰标志物,在各项临床应用中均发挥重要的作用,但其缺点在于不同临床情境下特异度并不一致。近年来,各种新型生物标志物不断问世,为心衰的诊断和治疗提供了更多的帮助。本专家共识基于国内外最新临床指南、专家共识以及临床研究,对目前已在临床应用的心衰生物标志物进行总结,希望能够为心衰生物标志物在临床的应用提供参考。     

Novel biomarkers in heart failure: usefulness in clinical practice

Biomarkers have become an increasingly important tool in clinical practice, helping to improve patient care. In heart failure (HF), brain natriuretic peptide and N-terminal prohormone of the brain natriuretic peptide have been widely applied in prognosis, clinical diagnosis and treatment. Recently, several novel biomarkers have been examined on their efficacy to improve diagnosis, determine the pathophysiologic state of HF, improve clinical decision making, clinical outcome, guide treatment and assess prognosis of HF patients. In this special report, the authors summarize the usefulness and significance of the most promising novel biomarkers in patients with HF.     

Sflt-1 in heart failure: relation with disease severity and biomarkers

Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors, such as placental growth factor (PlGF), which modulates cardiovascular (CV) remodeling. We determine sFlt-1 levels in patients with heart failure (HF) and its relationship to adverse cardiovascular (CV) events and biomarkers of cardiovascular risk. Levels of sFlt-1 and PlGF levels were also determined in healthy volunteers and patients with type 2 diabetes mellitus (T2DM). SFlt-1 and PlGF were clearly increased in HF patients in comparison to T2DM patients or healthy subjects (p?p?ρ?=?0.37, p?ρ?=?0.52, p?ρ?=?0.38, p?ρ?=?0.25, p?=?0.01) and PTH(1–84) (ρ?=?0.38, p?相似文献   

Emerging trends in the management of heart failure: Beta blocker therapy

There is overwhelming evidence that beta blocker therapy in the form of metoprolol, bisoprolol, and carvedilol can have positive outcomes on morbidity, mortality, and quality of life in patients who have been diagnosed with mild to severe heart failure. Barring contraindications, beta blockers should be considered a cornerstone of therapy for these patients along with ACE inhibitors and diuretics. Beta blocking drugs are effective in modifying the cascade of events that occur as a result of the neurohormonal response that leads to the devastating effects evident during heart failure. Long-term effects of beta blockade include an increase in cardiac output, an increase in exercise tolerance, a decrease in the number of hospitalizations, and an overall improvement in symptoms.     

Emerging biomarkers in chronic lung allograft dysfunction

ABSTRACT

Introduction: Lung transplantation remains an important treatment for patients with end stage lung disease. Chronic lung allograft dysfunction (CLAD) remains the greatest limiting factor for long term survival. As the diagnosis of CLAD is based on pulmonary function tests, significant lung injury is required before a diagnosis is feasible, likely when irreversible damage has already occurred. Therefore, research is ongoing for early CLAD recognition, with biomarkers making up a substantial amount of this research.

Areas covered: The purpose of this review is to describe available biomarkers, focusing on those which aid in predicting CLAD and distinguishing between different CLAD phenotypes. We describe biomarkers presenting in bronchial alveolar lavage (BAL) as well as circulating in peripheral blood, both of which offer an appealing alternative to lung biopsy.

Expert opinion: Development of CLAD involves complex, multiple immune and nonimmune mechanisms. Therefore, evaluation of potential CLAD biomarkers serves a dual purpose: clinically, the goal remains early detection and identification of patients at increased risk. Simultaneously, biomarkers offer insight into the different mechanisms involved in the pathophysiology of CLAD, leading to the development of possible interventions. The ultimate goal is the development of both preventive and early intervention strategies for CLAD to improve the overall survival of our lung transplant recipients.     

心力衰竭患者三种心肌细胞应激标志物的临床意义

目的本研究旨在通过监测心衰患者及对照组非心衰患者NT-pro-BNP、BNP、ST2的血浓度水平,探讨心衰患者三种心肌细胞应激标志物血浓度水平的变化及其临床意义。方法选择2009-10-2010-03期间在广州市第一人民医院心内科住院心力衰竭的患者84例,无心力衰竭的患者95例。结果心力衰竭患者BNP、NT-pro-BNP、ST2血浓度水平较对照组明显升高(P<0.01)。心衰患者三种标志物血浓度水平在不同心功能分级组间差异均有统计学意义(P<0.001)。NT-pro-BNP诊断心衰的AUCROC为0.957(95%CI0.917~0.997),BNP诊断心衰的AUCROC为0.868(95%CI0.803~0.933),ST2诊断心衰的AUCROC为0.758(95%CI0.669~0.846)。结论心力衰竭组患者三种心肌应激标志物血浓度水平对不同程度的HF评估,指导HF治疗、评价预后均具有重要临床价值;其中NT-pro-BNP诊断参考价值较大,而BNP次之,ST2有一定的参考作用。     

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure(CHF) which are independently associated with poor patient outcome.The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index(a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction.     

阿托伐他汀治疗对急性心力衰竭患者炎症标志物和急性肾损伤的影响

目的探讨阿托伐他汀治疗对急性心力衰竭(AHF)患者炎症标志物和急性肾损伤(AKI)的影响。方法选择2012年10月至2014年7月在惠州市仲恺高新区人民医院收治并诊断为AHF的患者92例,将其随机分为阿托伐他汀治疗组(46例)和对照组(46例)。治疗组入院后给予阿托伐他汀80 mg/d持续3 d,随后10 mg/d直至出院。对照组未给予他汀类药物治疗。主要终点事件为AKI发生和炎症标志物的改变。次要终点事件为院内和3个月随访期内全因病死率。结果治疗组患者AKI的发生率(13%)低于对照组AKI的发生率(15%),差异未见统计学意义(P=0.213)。两组患者的N端脑钠肽、超敏C-反应蛋白、胱抑素C水平比较差异未见统计学意义。同时,治疗组和对照组两组间的院内病死率(4.3%和3.8%,P0.999)和90 d随访全因病死率比较差异未见统计学意义。结论 AHF患者住院期间服用大剂量阿托伐他汀治疗可能是安全的,但对于降低炎症标志物和AKI是无效的。     

Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy

ABSTRACT: INTRODUCTION: This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy. METHODS: Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant). RESULTS: Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01). CONCLUSIONS: In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00595738.