In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Società Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).

AimsThough various neurohormonal systems are concurrently activated during heart failure (HF), their biological effectors are not always easy to measure due to their short life in vivo, instability in biological samples, or very low concentrations. We measured the plasma concentrations of four stable precursor fragments of neurohormonal systems in patients with chronic HF and evaluated their relationship with outcome. Methods and resultsThis study was performed in 1237 patients with chronic and stable HF enrolled in the GISSI-heart failure trial (GISSI-HF). The following four precursor fragments, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1) and C-terminal pro-vasopressin (CT-proAVP or copeptin), were measured at randomization and after 3 months. Baseline concentrations were independent predictors of clinical outcome (median follow-up 3.9 years). The addition of MR-proANP improved net reclassification for mortality when added to multivariable models based on clinical risk factors alone [net reclassification improvement (NRI) ¼ 0.12, P ¼ 0.0007] or together with NT-proBNP (NRI ¼ 0.06, P ¼ 0.01). Changes in MRproANP concentrations were related to mortality [HR (95% CI) 1.38 (0.99-1.93), P ¼ 0.0614 and 1.58 (1.13-2.21), P ¼ 0.0078 in the middle and highest vs. lowest tertiles], while changes in the other markers were not. ConclusionIn patients with chronic and stable HF enrolled in a multicentre, randomized, clinical trial, measurement of stable precursor fragments of vasoactive peptides provided prognostic information independent of natriuretic peptides which are currently the best biomarkers for risk stratification.--

on behalf of the GISSI-HF InvestigatorsBackground-Increased urinary excretion of albumin is an early sign of kidney damage and a risk factor for progressive cardiovascular and renal diseases and heart failure. There is, however, only limited information on the prevalence and prognostic role of urinary albumin excretion in patients with established chronic heart failure. Methods and Results-A total of 2131 patients enrolled in 76 sites participating in the GISSI-Heart Failure trial provided a first morning spot sample of urine at any of the clinical visits scheduled in the trial to calculate the urinary albumin-to-creatinine ratio. The relation between log-transformed urinary albumin-to-creatinine ratio and all-cause mortality (428 deaths, time from urine collection to event or censoring) was evaluated with Cox multivariable models adjusted for all significant risk factors at the time of urine collection, in the study population, and in patients without diabetes or hypertension. Almost 75% of the patients had normal urinary albumin excretion, but 19.9% had microalbuminuria (30 to 299 mg/g creatinine) and 5.4% had overt albuminuria (Ն300 mg/g). There was a progressive, significant increase in the adjusted rate of mortality in the study population (hazard ratio, 1.12; 95% CI, 1.05 to 1.18 per 1-U increase of log(urinary albumin-to-creatinine ratio), Pϭ0.0002) and in the subgroup of patients without diabetes or hypertension. Randomized treatments (n-3 polyunsaturated fatty acids or rosuvastatin) had no major impact on albumin excretion. Conclusions-Independently of diabetes, hypertension, or renal function, elevated albumin excretion is a powerful prognostic marker in patients with chronic heart failure. (Circ Heart Fail. 2010;3:65-72.)

PurposeTo evaluate the reduction over time of benign thyroid nodules treated using percutaneous laser ablation (PLA) and radiofrequency ablation (RFA) by the same equipe. Materials and MethodsNinety patients (age 55.6±14. 34,662.7±15,812.3 J in PLA vs. RFA group. Mean volume reduced from 20.3±16.4 ml to 13.17±10.74 ml (42%±17% reduction) at 1 month, 8.7±7.4 ml (60%±15% reduction) at 6 months and 7.1±7.7 ml (70%%±16% reduction) at 12 months In PLA group, and from 32.7±19.5 ml to 17.2±12.9 ml (51%±15% reduction) at 1 month, 12.8±9.6 ml (64±14% reduction) at 6 months and 9.9±9.2 ml (74%±14% reduction) at 12 months in RFA group. No difference in time course of the relative volume reduction between the two techniques was found. ConclusionsRFA and PLA are similarly feasible, safe and effective in treating benign thyroid nodules when performed by the same equipe. RFA is faster than PLA but require significantly higher energy.

In the CYCLE (CYCLosporinE A in Reperfused Acute Myocardial Infarction) trial, a single intravenous CsA bolus just before primary percutaneous coronary intervention had no effect on ST-segment resolution or hs-cTnT, and did not improve clinical outcomes or LV remodeling up to 6 months. (CYCLosporinE A in Reperfused Acute Myocardial Infarction [CYCLE]; NCT01650662; EudraCT number 2011-002876-18).

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Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant multisystemic disorders caused by expansion of microsatellite repeats. In both forms, the mutant transcripts accumulate in nuclear foci altering the function of alternative splicing regulators which are necessary for the physiological mRNA processing. Missplicing of insulin receptor (IR) gene (INSR) has been associated with insulin resistance, however, it cannot be excluded that post-receptor signalling abnormalities could also contribute to this feature in DM. We have analysed the insulin pathway in skeletal muscle biopsies and in myotube cultures from DM patients to assess whether downstream metabolism might be dysregulated and to better characterize the mechanism inducing insulin resistance. DM skeletal muscle exhibits alterations of basal phosphorylation levels of Akt/PKB, p70S6K, GSK3β and ERK1/2, suggesting that these changes might be accompanied by a lack of further insulin stimulation. Alterations of insulin pathway have been confirmed on control and DM myotubes expressing fetal INSR isoform (INSR-A). The results indicate that insulin action appears to be lower in DM than in control myotubes in terms of protein activation and glucose uptake. Our data indicate that post-receptor signalling abnormalities might contribute to DM insulin resistance regardless the alteration of INSR splicing.

Background Pediatric patients with atrioventricular valve disease have limited options for prosthetic valve replacement in sizes <15 mm. Based on successful experience with the stented bovine jugular vein graft (Melody valve) in the right ventricular outflow tract, the prosthesis has been modified for surgical valve replacement in pediatric patients with atrioventricular dysfunction with the intention of subsequent valve expansion in the catheterization laboratory as the child grows. Methods and Results A multicenter, retrospective cohort study was performed among patients who underwent atrioventricular valve replacement with Melody valve at 17 participating sites from North America and Europe, including 68 patients with either mitral (n=59) or tricuspid (n=9) replacement at a median age of 8 months (range, 3 days to 13 years). The median size at implantation was 14 mm (range, 9-24 mm). Immediately postoperatively, the valve was competent with low gradients in all patients. Fifteen patients died; 3 patients underwent transplantation. Nineteen patients required reoperation for adverse outcomes, including valve explantation (n=16), left ventricular outflow tract obstruction (n=1), permanent pacemaker implantation (n=1), and paravalvular leak repair (n=1). Twenty-five patients underwent 41 episodes of catheter-based balloon expansion, exhibiting a significant decrease in median gradient ( P<0.001) with no significant increase in grade of regurgitation. Twelve months after implantation, cumulative incidence analysis indicated that 55% of the patients would be expected to be free from death, heart transplantation, structural valve deterioration, or valve replacement. Conclusions The Melody valve is a feasible option for surgical atrioventricular valve replacement in patients with hypoplastic annuli. The prosthesis shows acceptable short-term function and is amenable to catheter-based enlargement as the child grows. However, patients remain at risk for mortality and structural valve deterioration, despite adequate early valvular function. Device design and implantation techniques must be refined to reduce complications and extend durability. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02505074.