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      Emerging Biomarkers in Heart Failure and Cardiac Cachexia

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          Abstract

          Biomarkers are objective tools with an important role for diagnosis, prognosis and therapy optimization in patients with heart failure (HF). To date, natriuretic peptides are closest to optimal biomarker standards for clinical implications in HF. Therefore, the efforts to identify and test new biomarkers in HF are reasonable and justified. Along the natural history of HF, cardiac cachexia may develop, and once at this stage, patient performance and prognosis is particularly poor. For these reasons, numerous biomarkers reflecting hormonal, inflammatory and oxidative stress pathways have been investigated, but only a few convey relevant information. The complex pathophysiology of HF appears far too complex to be embraced by a single biomarker; thus, a combined approach appears reasonable. With these considerations, we have reviewed the recent developments in the field to highlight key candidates with diagnostic, prognostic and therapy optimization properties, either alone or in combination.

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          Most cited references96

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          Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline.

          The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy. The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders. The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.
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            ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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              The war against heart failure: the Lancet lecture.

              Heart failure is a global problem with an estimated prevalence of 38 million patients worldwide, a number that is increasing with the ageing of the population. It is the most common diagnosis in patients aged 65 years or older admitted to hospital and in high-income nations. Despite some progress, the prognosis of heart failure is worse than that of most cancers. Because of the seriousness of the condition, a declaration of war on five fronts has been proposed for heart failure. Efforts are underway to treat heart failure by enhancing myofilament sensitivity to Ca(2+); transfer of the gene for SERCA2a, the protein that pumps calcium into the sarcoplasmic reticulum of the cardiomyocyte, seems promising in a phase 2 trial. Several other abnormal calcium-handling proteins in the failing heart are candidates for gene therapy; many short, non-coding RNAs--ie, microRNAs (miRNAs)--block gene expression and protein translation. These molecules are crucial to calcium cycling and ventricular hypertrophy. The actions of miRNAs can be blocked by a new class of drugs, antagomirs, some of which have been shown to improve cardiac function in animal models of heart failure; cell therapy, with autologous bone marrow derived mononuclear cells, or autogenous mesenchymal cells, which can be administered as cryopreserved off the shelf products, seem to be promising in both preclinical and early clinical heart failure trials; and long-term ventricular assistance devices are now used increasingly as a destination therapy in patients with advanced heart failure. In selected patients, left ventricular assistance can lead to myocardial recovery and explantation of the device. The approaches to the treatment of heart failure described, when used alone or in combination, could become important weapons in the war against heart failure.
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                Author and article information

                Contributors
                Role: External Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                22 December 2014
                December 2014
                : 15
                : 12
                : 23878-23896
                Affiliations
                [1 ]Clinical Hospital Zvezdara, Cardiology Department, Dimitrija Tucovica 161, Belgrade 11000, Serbia; E-Mails: loncar_goran@ 123456yahoo.com (G.L.); ncvetinovic@ 123456gmail.com (N.C.); drarandjelovic@ 123456yahoo.com (A.A.)
                [2 ]National Institute of Public Health, Ljubljana 1000, Slovenia; E-Mail: dane.omersa@ 123456gmail.com
                [3 ]School of Medicine, University of Belgrade, Belgrade 11000, Serbia
                [4 ]Department of Cardiology, General Hospital Celje, Oblakova 5, Celje 3000, Slovenia
                [5 ]Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: mitja.lainscak@ 123456guest.arnes.si ; Tel.: +386-3137-9533; Fax: +386-3423-3666.
                Article
                ijms-15-23878
                10.3390/ijms151223878
                4284795
                25535078
                05cdea14-6dcf-48fb-9409-457e86c4c5bf
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 November 2014
                : 11 December 2014
                : 11 December 2014
                Categories
                Review

                Molecular biology
                heart failure,cardiac cachexia,emerging biomarkers
                Molecular biology
                heart failure, cardiac cachexia, emerging biomarkers

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