Thyroid (Dys)Function in Heart Failure: Is it a Potential Target for Medical Treatment?

Alessandro Pingitore, Giorgio IervasiInstitute of Clinical Physiology, CNR, Pisa, ItalyIntroductionCurrently, there is little doubt that activation of the neuroendocrine (NE) system is predominately responsible for the progressive decline of heart function in heart failure (HF). This is due to the complex action of neurotransmitters, hormonal factors, and/or immunological pathways. Evidence that supports this point of view is the clear prognostic benefit and the reduction of HF progression by using NE-guided therapeutic approaches (SOLVD investigators 1992; Eichhorn and Bristow 1996; Packer et al 1996; Opie 2004; Solomon et al 2004). However, the fact that HF represents one of the major causes of morbidity and mortality in Western countries also suggests that the current portfolio of NE antagonists fails to completely explain and possibly counteract disease progression (Guyatt and Deveraux 2004). In this context, interest in the relationship between thyroid hormones (THs) and HF is increasingly gaining prominence. The chief reason for the latter is the emerging novel actions of THs on the cardiovascular system and, more specifically, the role of TH as a prognostic biomarker of cardiac disease as well as the potential benefit of TH administration in patients with HF

Thyroid hormone and heart failure: from myocardialprotection to systemic regulation

Heart failure (HF) is an intriguing model of chronic disease. It starts as an organ disorder developing, in its progression, into a systemic disease in which the dysfunction of other organs plays a relevant clinical and prognostic impact. Furthermore, continuous activation of systemic pathways plays a role in disease progression, switching their effect from protective to harmful. In this combination of organ dysfunction and systemic derangement, thyroid hormone (TH) have an important regulative impact from cardiovascular to systemic level and from molecular/cellular processes to clinical setting. Whether it is accepted to include TH and thyroid stimulating hormone assessment in the clinical HF course, the next challenge will be to ascertain the benefit of TH replacement therapy in HF patients, taking into consideration the type of hormone to administer, dosage and treatment schedule

Thyroid Hormone and Cardiac Disease: From Basic Concepts to Clinical Application

Nature's models of regeneration provide substantial evidence that a natural healing process may exist in the heart. Analogies existing between the damaged myocardium and the developing heart strongly indicate that regulatory factors which drive embryonic heart development may also control aspects of heart regeneration. In this context, thyroid hormone (TH) which is critical in heart maturation during development appears to have a reparative role in adult life. Thus, changes in TH -thyroid hormone receptor (TR) homeostasis are shown to govern the return of the damaged myocardium to the fetal phenotype. Accordingly, thyroid hormone treatment preferentially rebuilds the injured myocardium by reactivating developmental gene programming. Clinical data provide further support to this experimental evidence and changes in TH levels and in particular a reduction of biologically active triiodothyronine (T3) in plasma after myocardial infarction or during evolution of heart failure, are strongly correlated with patients morbidity and mortality. The potential of TH to regenerate a diseased heart has now been testing in patients with acute myocardial infarction in a phase II, randomized, double blind, placebo-controlled study (the THiRST study)

A new Web-based medical tool for assessment and prevention of comprehensive cardiovascular risk

Daniele Franchi1,2, Davide Cini1, Giorgio Iervasi11Istituto di Fisiologia Clinica, CNR, Pisa, Italy; 2Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina, Università di Pisa, Pisa, ItalyBackground: Multifactor cardiovascular disease is the leading cause of death; besides well-known cardiovascular risk factors, several emerging factors such as mental stress, diet type, and physical inactivity, have been associated to cardiovascular disease. To date, preventive strategies are based on the concept of absolute risk calculated by different algorithms and scoring systems. However, in general practice the patient's data collection represents a critical issue.Design: A new multipurpose computer-based program has been developed in order to:1) easily calculate and compare the absolute cardiovascular risk by the Framingham, Procam, and Progetto Cuore algorithms; 2) to design a web-based computerized tool for prospective collection of structured data; 3) to support the doctor in the decision-making process for patients at risk according to recent international guidelines.Methods: During a medical consultation the doctor utilizes a common computer connected by Internet to a medical server where all the patient's data and software reside. The program evaluates absolute and relative cardiovascular risk factors, personalized patient's goals, and multiparametric trends, monitors critical parameter values, and generates an automated medical report.Results: In a pilot study on 294 patients (47% males; mean age 60 ± 12 years [± SD]) the global time to collect data at first consultation was 13 ± 11 minutes which declined to 8 ± 7 minutes at the subsequent consultation. In 48.2% of cases the program revealed 2 or more primary risk factor parameters outside guideline indications and gave specific clinical suggestions to return altered parameters to target values.Conclusion: The web-based system proposed here may represent a feasible and flexible tool for clinical management of patients at risk of cardiovascular disease and for epidemiological research.Keywords: internet, informatics, cardiovascular risk, evidence-based practice, medical consultation, decision support, clinical information system

Valutazione delle prestazioni analitiche dei metodi per la misura di Tg, AbTg e AbTPO: risultati del programma di VEQ Tg-check

Not availableIl programma di Valutazione Esterna di Qualit? Tg-check ? attivo da 5 anni; i laboratori nel ciclo 2008 sono 110 e circa il 70% di questi partecipa trasmettendo i risultati via internet collegandosi al sito web dei programmi di VEQ EQAS-CNR (http:/eqas.ifc.cnr.it). Dall\u27analisi cumulativa dei risultati dei 6 esercizi di controllo del ciclo 2007 risulta che i metodi per la misura della Tireoglobulina (Tg), nonostante l\u27uso di standard calibrati verso la stessa preparazione di riferimento (1? IRP CRM 457), continuano a produrre risultati molto diversi tra loro in particolare nei campioni contenenti anticorpi AbTg. In questi campioni, la variabilit? totale (CV tra-laboratori, tra-metodi) osservata nella VEQ ? molto elavata (74-83%) a causa dell\u27interferenza degli anticorpi endogeni nella misura della Tg; ? noto infatti che, ad oggi, tutti i metodi risultano pi? o meno interferiti dalla presenza di AbTg nel campione e questo provoca l\u27allargamento delle differenze sistematiche tra metodi. Nei campioni negativi per AbTg, invece, le differenze sistematiche tra metodi si riducono notevolmente (CV tra-laboratori, tra-metodi 20-40%)

RISK ASSESSMENT IN PET RADIOPHARMACEUTICALS PRODUCTION: PLANNING THE IMPLEMENTATION OF A PRODUCTION LINE COMPLIANT WITH GMP REGULATION

The aim of this paper is to provide some indications for carrying out the risk assessment for the activation of a production line of a radiopharmaceutical containing a positrons emitting radionuclide. The risk analysis was performed by following the ICH Q10 guideline and ISO 9001:2015 standards and by using the risk-based thinking approach applied to the entire production cycle. The overall analysis has shown that hard and soft skills of the expert group are key factors of success both in technical and radiopharmaceuticals-related preparations as well as in risk management methodologies

Echocardiographic nomograms for chamber diameters and areas in Caucasian children

BACKGROUND: Although a quantitative evaluation of cardiac chamber dimensions in pediatric echocardiography is often important, nomograms for these structures are limited. The aim of this study was to establish reliable echocardiographic nomograms of cardiac chamber diameters and areas in a wide population of children. METHODS: A total of 1,091 Caucasian Italian healthy children (age range, 0 days to 17 years; 44.8% female) with body surface areas (BSAs) ranging from 0.12 to 1.8 m(2) were prospectively enrolled. Twenty-two two-dimensional and M-mode measurements of atrial and ventricular chamber diameters and areas were performed. Models using linear, logarithmic, exponential, and square-root relationships were tested. Heteroscedasticity was tested by the White test and the Breusch-Pagan test. Age, weight, height, and BSA, calculated by the Haycock formula, were used as the independent variables in different analyses to predict the mean value of each echocardiographic measurement. The influence of various confounders, including gender, type of delivery, prematurity, and interobserver variability, was also evaluated. Structured Z scores were then computed. RESULTS: The Haycock formula provided the best fit and was used when presenting data as predicted values (mean ? 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. Confounders were not included in the final models, because they did not show significant effects for most of the measurements. CONCLUSIONS: Echocardiographic reference values are presented for chamber area and diameters, derived from a large population of healthy children. These data partly cover a gap in actual pediatric echocardiographic nomograms. Further studies are required to reinforce these data, as well as to evaluate other parameters and ethnicities

Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors.

BACKGROUND: The routine use of brain natriuretic peptide (BNP) in pediatric cardiac surgery remains controversial. Our aim was to test whether BNP adds information to predict risk in pediatric cardiac surgery. METHODS: In all, 587 children undergoing cardiac surgery (median age 6.3 months; 1.2-35.9 months) were prospectively enrolled at a single institution. BNP was measured pre-operatively, on every post-operative day in the intensive care unit, and before discharge. The primary outcome was major complications and length ventilator stay \u3e15 days. A first risk prediction model was fitted using Cox proportional hazards model with age, body surface area and Aristotle score as continuous predictors. A second model was built adding cardiopulmonary bypass time and arterial lactate at the end of operation to the first model. Then, peak post-operative log-BNP was added to both models. Analysis to test discrimination, calibration, and reclassification were performed. RESULTS: BNP increased after surgery (p CONCLUSIONS: Our data indicates that BNP may improve the risk prediction in pediatric cardiac surgery, supporting its routine use in this setting