Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: Results of the forward (randomized trial to assess efficacy of pufa for the maintenance of sinus rhythm in persistent atrial fibrillation) trial
MacChia A.,Fundacion GESICA |
Grancelli H.,Fundacion GESICA |
Varini S.,Fundacion GESICA |
Nul D.,Fundacion GESICA |
And 8 more authors.
Journal of the American College of Cardiology | Year: 2013
Objectives: The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. Background: Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. Methods: This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. Results: There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). Conclusions: Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220) © 2013 American College of Cardiology Foundation.
Rossignol P.,French Institute of Health and Medical Research |
Rossignol P.,University of Lorraine |
Masson S.,Istituto di Ricerche Farmacologiche Mario Negri |
Barlera S.,Istituto di Ricerche Farmacologiche Mario Negri |
And 13 more authors.
European Journal of Heart Failure | Year: 2015
Aims Uncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W-LOSS) in chronic heart failure (HF) patients. We assessed whether W-LOSS added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W-LOSS were studied. Methods and results W-LOSS and estimated plasma volume changes were measured serially in the GISSI-HF (n = 6820) and Val-HeFT trials (n = 4892). In both studies, experiencing at least one episode of ≥5% W-LOSS during the first year of follow-up was considered a sign of wasting. In GISSI-HF, self-reported unintentional W-LOSS ≥2 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W-LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI-HF and Val-HeFT, respectively (unintentional ≥2 kg W-LOSS occurred in 18.9% in GISSI-HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W-LOSS was found to be independently associated with mortality and adverse cardiovascular and non-cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W-LOSS was independently associated with several features representing the severity of HF, including baseline NT-proBNP and high sensitivity C-reactive protein (hsCRP) in Val-HeFT. Conclusions W-LOSS was a frequent finding in the GISSI-HF and Val-HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.
Benvenga S.,Messina University |
Pintaudi B.,Fondazione Mario Negri Sud |
Vita R.,Messina University |
Di Vieste G.,Messina University |
Di Benedetto A.,Messina University
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: Autoimmune thyroid diseases (AITDs) can be associated with type 1 diabetes (DM1). The prevalence of serum antibodies against thyroid hormones (THAb) in subjects with autoimmune diseases other than DM1 is increasing. No data are available for DM1. Objective: The objectives were evaluate the rate of associated AITD; the rate of positiveness for serum THAb; the panel of THAb based on thyroid hormone interaction and on Ig class; and the association of AITD alone, THAb alone, or AITD plus THAb with diabetes-related complications. Design: This was an observational, prospective study with 6-year (2005-2011) follow-up. Setting: The setting was an outpatient diabetes clinic. Patients: Fifty-two consecutive subjects (53.8% males; mean age, 37.4 ± 7.4 y; diabetes duration, 19.9 ± 8.2 y) with DM1. All participants completed the study. Main Outcome Measures: Main outcome measures were AITD rate; THAb positivity according to hormone interaction and Ig class; association of AITD and THAb with diabetes-related complications. Results: AITD rate increased from baseline (34.6%) to follow-up (38.5%). Subjects with DM1 had a high prevalence of THAb (92.3%). The presence of AITD at baseline was associated with subsequent development of macroangiopathy (0 vs 33% at baseline and follow-up, respectively; P = .029). Some THAb patterns, the majority having T3 binding in common, were associated with the progression and development of diabetes-related complications. Conclusions: THAb synthesis in DM1 might be driven by increased glycosylation of thyroglobulin. Anti T3-THAb may cause a relative "tissue hypothyroidism" by sequestering thyroid hormone, this at least partially contributing to worsening diabetes-related vascular complications. In a clinical setting THAb positivity could identify subjects more likely to develop diabetes complications. Copyright © 2015 by the Endocrine Society.
Vespasiani G.,Diabetes Unit |
Rossi M.C.,Fondazione Mario Negri Sud
Frontiers in Diabetes | Year: 2015
A flexible therapy for type 1 diabetes based on carbohydrate counting and insulin dose adjustment can promote glycemic control and quality of life without worsening severe hypoglycemia or cardiovascular risk. The complexity of the standard education required by the flexible therapy can be managed with the 'Diabetes Interactive Diary (DID)', a carbohydrate/bolus calculator for mobile phones. It also works as a telemedicine system based on communication between patient and physician via text messages (SMS). The efficacy and safety of the DID have been tested in 3 main studies. The DID was demonstrated to be effective in improving metabolic control as well as standard education while ensuring several additional benefits. First, it halved the time dedicated to education and simplified the calculation of carbohydrates content and insulin doses, allowing more individuals with type 1 diabetes to adopt the flexible regimen. Second, the use of the DID was also associated with an 86% decrease in risk of grade 2 hypoglycemia. Additionally, several quality of life scales were significantly improved, suggesting that the use of telemedicine can increase the acceptance of insulin treatment and help patients cope with the disease. Currently, the DID is available as a free app for smartphones. © 2015 S. Karger AG, Basel.
Degirolamo C.,National Cancer Research Center |
Rainaldi S.,Fondazione Mario Negri Sud |
Bovenga F.,National Cancer Research Center |
Murzilli S.,Fondazione Mario Negri Sud |
And 2 more authors.
Cell Reports | Year: 2014
Gut microbiota influences host health status by providing trophic, protective, and metabolic functions, including bile acid (BA) biotransformation. Microbial imprinting on BA signature modifies pool size and hydrophobicity, thus contributing to BA enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut microbiota modulation induced by VSL#3 probiotics enhances BA deconjugation and fecal excretion in mice. These events are associated with changes in ileal BA absorption, repression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, and increased hepatic BA neosynthesis. Treatment with a FXR agonist normalized fecal BA levels in probiotic-administered mice, whereas probiotic-induced alterations in BA metabolism are abolished upon FXR and FGF15 deficiency. Our data provide clear invivo evidence that VSL#3 probiotics promote ileal BA deconjugation with subsequent fecal BA excretion and induce hepatic BA neosynthesis via downregulation of the gut-liver FXR-FGF15 axis. © 2014 The Authors.