Diagnostic accuracy and prognostic relevance of the measurement of the cardiac natriuretic peptides: a review

Summary Background Pathophysiological and clinical relevance of cardiac natriuretic hormone (CNH) assay has been investigated by a great deal of experimental and clinical studies. Authors sought to evaluate the diagnostic accuracy and prognostic relevance of the measurement of CNHs according to the evidence-laboratory medicine principles. Methods In June 2003, a computerized literature search on National Library of Medicine using keyword "ANP" and "BNP" found more than 12.300 and 1200 articles, respectively. A more refined search with keywords "ANP or BNP assay" extracted about 7000 and 800 articles, respectively. Only studies specifically designed to evaluate the diagnostic accuracy and prognostic relevance of CNH measurement were selected from this huge mass of articles to be discussed in this review. Content Several studies suggested that CNH assay may be clinically useful: for the screening and classification of patients with heart failure, as a prognostic marker in cardiovascular disease, in the follow-up of patients with heart failure, and also because it may reduce the need for further cardiac investigation. However, it is difficult to compare, even the best well-designed studies, because not only they evaluated different populations, but they also used different gold standards. Conclusions CNH assay and conventional diagnostic work-up provide complementary information for the evaluation of presence and severity of cardiac dysfunction and clinical disease. Several aspects of CNH assay are still to be delucidated, and further work is still needed to carefully assess its diagnostic accuracy and prognostic value in cardiac disease

Biomarkers for sepsis: an unfinished journey

none2noneClerico A;Plebani MClerico, A; Plebani, Mari

The 99th percentile of reference population for cTnI and cTnT assay: Methodology, pathophysiology and clinical implications

According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision â\u89¤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines

Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications

The discovery of cardiac natriuretic hormones required a profound revision of the concept of heart function. The heart should no longer be considered only as a pump, but rather as a multi-functional and interactive organ, part of a complex network and active component of the integrated systems of the body. In the present review, we will first consider the cross-talk between endocrine and contractile function of the heart. Then, based on the existing literature, we will propose the hypothesis that cardiac endocrine function is an essential component of the integrated systems of the body and thus plays a pivotal role in fluid, electrolyte and hemodynamic homeostasis. We will highlight those studies indicating how alterations in cardiac endocrine function can better explain the pathophysiology of cardiovascular diseases and in particular of heart failure, in which several target organs develop a resistance to the biological action of cardiac natriuretic peptides. Finally, we will emphasize the concept that a complete knowledge of the cardiac endocrine function and of its relation with other neurohormonal regulatory systems of the body is crucial to correctly interpret changes in circulating natriuretic hormones, especially the brain natriuretic peptide