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

Critical Comparison of Documents From Scientific Societies on Cardiac Amyloidosis: JACC State-of-the-Art Review.

Over the last year, 5 national or international scientific societies have issued documents regarding cardiac amyloidosis (CA) to highlight the emerging clinical science, raise awareness, and facilitate diagnosis and management of CA. These documents provide useful guidance for clinicians managing patients with CA, and all include: 1) an algorithm to establish a diagnosis; 2) an emphasis on noninvasive diagnosis with the combined use of bone scintigraphy and the exclusion of a monoclonal protein; and 3) indications for novel disease-modifying therapies for symptomatic CA, either with or without peripheral neuropathy. Nonetheless, the documents diverge on specific details of diagnosis, risk stratification, and treatment. Highlighting the similarities and differences of the documents by the 5 scientific societies with respect to diagnosis, risk stratification, and treatment offers useful insight into the knowledge gaps and unmet needs in the management of CA. An analysis of these documents, therefore, highlights “gray zones” requiring further investigation.post-print2330 K

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

The potential roles of gamma-glutamyltransferase activity in the progression of atherosclerosis and cardiovascular diseases.

The oxidation of low density lipoproteins (LDL) is regarded as a critical factor in the pathogenesis of atherosclerosis, especially the initial steps of the disease. In addition, other oxidative events have been shown to participate in the progression of atherosclerosis and precipitation of cardiovascular events, through modulation of important components of lesions of the vessel wall (smooth muscle cell proliferation, protease/antiprotease balance, endothelial functions). Our recent studies have provided evidence that the enzyme gamma-glutamyltransferase (GGT), normally found in serum, is often accumulated within the plaque environment in substantial amounts, and that this activity is a potential source of a variety of prooxidant species. Concurrently, epidemiological research has conclusively documented that the serum levels of GGT are an independent factor in prognosis of myocardial infarction and stroke in atherosclerotic patients. Several signs suggest that the GGT appearing in plaque tissue may originate from the serum enzyme, which in facts associates with the circulating lipoprotein fractions. Thus, data seem to point out that pathogenesis of atherosclerosis – and in particular of the events leading to progression of the disease and acute cardiovascular events – might include an as yet unexplored pathway, based on the prooxidant effects of gamma-glutamyltransferase accumulating as a result of LDL entry in the vessel wall

Evaluation of the expression of transcripts coding for CNP and for its specific receptor, NPR-B, by Real Time PCR in cardiac tissue of normal and heart failure animals

Purpose: Higher plasma levels and a cardiac production of C-type natriuretic peptide (CNP) were recently observed in patients with chronic heart failure (HF), but its cellular source and possible difference between atrium and ventricle expression are so far lacking. Aim of this study was to evaluate the expression of transcripts coding for CNP and for its specific receptor, NPR-B, in cardiac tissue (right and left atrium and ventricle) of normal and CHF animals. CNP tissue levels were also determined in cardiac extracts. Methods: Adult male minipigs (n=5) were chronically instrumented with a unipolar pacemaker connected to the anterior left ventricular (LV) wall. HF was induced by rapid pacing (180 beats/min) for 4 weeks. End-stage HF occurred at 24?2 days of pacing when the LV end-diastolic pressure was !25 mmHg. As control, we studied 5 adult male minipigs. At 4 weeks, myocardial samples were collected. Both CNP mRNA and proteins were extracted from a same sample with the method of phenol/guanidine-thiocyanate/chloroform. Tissue CNP levels were determined by a radioimmunoassay after a preliminary extraction on Sep-Pak C18, while the expression of mRNA coding for CNP and NPR-B in myocardial tissue (n=40) by Real Time reverse transcriptase-polymerase chain reaction (PCR) with DDCt method. As overall control, a parallel Real Time-PCR assay for BNP mRNA expression was carried out in the same samples. Real Time-PCR analysis was performed using an automated sequence instrument (7900HT Fast, Applied Biosystems) for the real-time monitoring of nucleic acid green dye fluorescence (SYBR Green I). Results: As to myocardial extracts, CNP was found in all cardiac chambers of controls and its content was ten fold higher in atria than in ventricles (RA: 13.7?1.9 pg/mg; LA: 8.7?3.8 pg/mg; RV: 1.07?0.33 pg/mg; LV: 0.93?0.17 pg/mg). At 4 weeks of pacing stress, myocardial levels of CNP in LV were higher than in controls (15.8?9.9 pg/mg vs.0.9?0.17 pg/mg, p=0.01). The expression of mRNA coding for CNP was higher at 4 weeks of pacing althought CNP gene expression appears to be noticeable lower than that of BNP. The NPR-B resulted to be expressed in all cardiac regions analyzed, and a down-regulation was observed in ventricles after HF. Althought further investigations are necessary, the high tissue levels of CNP found after pacing stress as well as the myocardial CNP and NPR-B expression suggest an important role of this peptide in a so complex pathology as HF