Duration of Untreated Cardiac Arrest and Clinical Relevance of Animal Experiments : The Relationship Between the “No-Flow” Duration and the Severity of Post-Cardiac Arrest Syndrome in a Porcine Model

INTRODUCTION: The study investigated the effect of untreated cardiac arrest (CA), i.e. \u201cno-flow\u201d time, on post-resuscitation myocardial and neurological injury, and survival in a pig model to identify an optimal duration that adequately reflects the most frequent clinical scenario. METHODS:: An established model of myocardial infarction followed by CA and cardiopulmonary resuscitation was used. Twenty-two pigs were subjected to 3 no-flow durations: short (8\u201310?min); intermediate (12\u201313?min); and long (14\u201315?min). Left ventricular ejection fraction (LVEF) was assessed together with thermodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT). Neurological impairment was evaluated by neurological scores, serum neuron specific enolase (NSE), and histopathology. RESULTS:: More than 60% of animals survived when the duration of CA was 6413?min, compared to only 20% for a duration 6514?min. Neuronal degeneration and neurological scores showed a trend towards a worse recovery for longer no-flow durations. No animals achieved a good neurological recovery for a no-flow 6514?min, in comparison to a 56% for a duration 6413?min (p?=?0.043). Serum NSE levels significantly correlated with the no-flow duration (r?=?0.892). Longer durations of CA were characterized by lower LVEF and CO compared to shorter durations (p?<?0.05). The longer was the no-flow time, the higher was the number of defibrillations delivered (p?=?0.043). The defibrillations delivered significantly correlated with LVEF and plasma hs-cTnT. CONCLUSIONS:: Longer no-flow durations caused greater post-resuscitation myocardial and neurological dysfunction and reduced survival. An untreated CA of 12\u201313?min may be an optimal choice for a clinically relevant model

NT-proBNP for Risk Prediction in Heart Failure:Identification of Optimal Cutoffs Across Body Mass Index Categories

OBJECTIVES The goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories. BACKGROUND  Concentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain. METHODS Individual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI = 40 kg/m(2)) obese. The prognostic rote of NT-proBNP was tested for the endpoints of all-cause and cardiac death. RESULTS The study population included 12,763 patients (mean age 66 +/- 12 years; 25% women; mean left ventricular ejection fraction 33% 113%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (beta = -0.174 for 1 kg/m(2); P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men. CONCLUSIONS NT-proBNP maintains its independent prognostic value up to 40 kg/m(2) BMI, and tower optimal risk-prediction cutoffs are observed in overweight and obese patients

Histone Deacetylase Inhibition Enhances Self Renewal and Cardioprotection by Human Cord Blood-Derived CD34+ Cells

Abstract BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs), have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs) is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+) were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+) cells with enhanced self renewal and cardioprotection

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Incretin-based drugs and hospitalization for heart failure in the clinical practice: A nested case-control study

Background and aims: There are concerns that incretin-based antidiabetic drugs - including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists -increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting. Methods and results: Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry. The multivariate odds ratios (ORs) of HF in relation to current use of incretin-based drugs as compared to current use of two or more oral antidiabetics was 1.06 (95% confidence interval, CI, 0.83-1.35), with no evidence of a trend in risk with increasing duration of use. The corresponding ORs were 1.10 (95% CI 0.85-1.41) for DPP-4 inhibitors and 0.84 (95% CI 0.48-1.47) for GLP-1 receptor agonists. Estimates were consistent in various sensitivity analyses. Conclusions: This study indicates that incretin-based drugs are not associated with an increased risk of hospitalization for HF, thus providing further reassurance on the cardiovascular safety of these antidiabetic drugs in the clinical practice.