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

Piloting a web-based systematic collection and reporting of patient-reported outcome measures and patient-reported experience measures in chronic heart failure

OBJECTIVES: To evaluate the feasibility of a digital and continuous collection and reporting of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) for chronic heart failure (CHF). DESIGN: A single-site pilot study was settled for evaluating the feasibility of the intervention, both using qualitative and quantitative data (ie, workshop, surveys). SETTING: The pilot has been implemented in a Tuscan specialised hospital (Italy). PARTICIPANTS: 162 patients were involved. Inclusion criteria were: a previous diagnosis of HF, age ≥18 years, absence of cognitive impairment or active tumours, ability to provide informed consent to study participation. INTERVENTION: The continuous collection and reporting of PROMs and PREMs has been designed and implemented in 2018. PREMs questionnaires for patients were developed, while Kansas City Cardiomyopathy Questionnaire-12 was used for assessing PROMs. Questionnaires are administered at specific time points: discharge; 30 days, 7 and 12 months after the discharge. Enrolment of patients, administration and real-time reporting of questionnaires are carried on through a digital platform. OUTCOME MEASURES: Enrolment, response and drop-out rates were considered to assess the feasibility of the intervention. Qualitative data were collected during meetings and workshops with health workers. The representativeness of the recruited sample with respect to the population characteristics was also evaluated. RESULTS: The system has been successfully implemented during 2018. Response rates have been consistently above 50%, demonstrating patients' transversal willingness to participate. All the involved stakeholders acknowledged the feasibility of the design. The recruited sample is significantly different in terms of age and educational level compared with the overall population characteristics. CONCLUSION: It is possible to run a web-based systematic collection and reporting system for CHF patient-reported data. Systematic collection and reporting of PROMs and PREMs data allows professionals to increasingly assume CHF patient perspective in their daily work. Limitations will be used to improve the system

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