217 Six-hour holter recording of microvolt T-wave alternans and heart rate turbulence in the CCU compared to classical 24-hour ambulatory ECG

BackgroundT-wave alternans (TWA) and heart rate turbulence (HRT) measured during 24 hour-ECG recordings are 2 powerful non-invasive tools to risk-stratify cardiovascular patients. The aim of our study is to assess whether a fast ECG-holter scan yields different information from classical 24-hour ambulatory ECG regarding TWA and HRT measurements.MethodsAll consecutive 21 patients with a non-ST-elevated myocardial infarction and admitted in intensive care unit of cardiology, have been monitored with an ECG-holter for classical, TWA and HRT analysis over 24 hours. TWA has been measured with the modified moving average method. Routine reading of the holters has been followed by a specific analysis. Each 24-hour period has been divided into four equal periods. Maximal TWA, T-onset and T-slope for HRT over those four 6-hour periods have been analyzed and compared with full day results using a repeated measures analysis of variance (ANOVA).Results16 men and 5 women aged between 31 and 90 (mean 57.5 +/− 24.8) have been included. Mean maximal TWA was 73±25μV. 6-hour maximal TWA was 59 +/− 23μV, 55 +/− 26μV, 56 +/− 30.01 and 48 +/− 23.27μV (p=0.11). HRT as assessed by T onset and T slope were −0.00619% +/− 0.02, 0.00333% +/− 0.04, 0.00571% +/− 0.03, −0.00952% +/− 0.03 (p=0.46) and 3.75 +/− 3.99, 5.46 +/− 7.29, 6.32 +/− 9.13, 5.96 +/− 10.85 (p=0.46) respectively for each time period.ConclusionThis preliminary study suggests that a 6-hour ECG-Holter recording could be a reliable and feasible method to assess cardiovascular mortality and risk of SCD in patients admitted for an acute coronary syndrome in intensive care unit by studying TWA and HRT. Faster risk stratification could thus be done during hospitalization in order to optimize therapeutics and better identify candidate for fast ICU discharge

Candidate gene resequencing in a large bicuspid aortic valve-associated thoracic aortic aneurysm cohort: SMAD6 as an important contributor

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Although many BAV patients remain asymptomatic, at least 20% develop thoracic aortic aneurysm (TAA). Historically, BAV-related TAA was considered as a hemodynamic consequence of the valve defect. Multiple lines of evidence currently suggest that genetic determinants contribute to the pathogenesis of both BAV and TAA in affected individuals. Despite high heritability, only very few genes have been linked to BAV or BAV/TAA, such as NOTCH1, SMAD6, and MAT2A. Moreover, they only explain a minority of patients. Other candidate genes have been suggested based on the presence of BAV in knockout mouse models (e.g., GATA5, NOS3) or in syndromic (e.g., TGFBR1/2, TGFB2/3) or non-syndromic (e.g., ACTA2) TAA forms. We hypothesized that rare genetic variants in these genes may be enriched in patients presenting with both BAV and TAA. We performed targeted resequencing of 22 candidate genes using Haloplex target enrichment in a strictly defined BAV/TAA cohort (n = 441; BAV in addition to an aortic root or ascendens diameter = 4.0 cm in adults, or a Z-score = 3 in children) and in a collection of healthy controls with normal echocardiographic evaluation (n = 183). After additional burden analysis against the Exome Aggregation Consortium database, the strongest candidate susceptibility gene was SMAD6 (p = 0.002), with 2.5% (n = 11) of BAV/TAA patients harboring causal variants, including two nonsense, one in-frame deletion and two frameshift mutations. All six missense mutations were located in the functionally important MH1 and MH2 domains. In conclusion, we report a significant contribution of SMAD6 mutations to the etiology of the BAV/TAA phenotype

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Mechanism related to reduction of intraocular pressure by melanocortins in rabbits

AIM—To investigate whether the ocular hypotensive effect of alpha melanocyte stimulating hormone (MSH) is related to eicosanoids or cyclic AMP (cAMP).
METHODS—Intraocular pressure (IOP) readings were taken at a similar time on the day before and after a single dose of topical MSH. Changes in the levels of prostaglandin E(2) (PGE(2)) and prostacyclin in incubated iris ciliary body (ICB) explants were measured by specific radioimmunoassay (RIA). Incubated ICB explants were exposed to MSH or adrenaline (epinephrine) for a week. In addition, cAMP levels in the medium were determined following short term incubation using RIA.
RESULTS—A significant dose related reduction in IOP was noted with topical MSH (mean (SD) maximal effect 4.5 (0.1) mm Hg (21%); p<0.001 v appropriate baseline) which persisted up to 6 hours (p=0.05). MSH treated ICB explants showed a 1.5-fold increase in PGE(2) and prostacyclin levels (p<0.001 for each parameter) while cAMP levels were increased twofold (p<0.001).
CONCLUSIONS—A single application of MSH caused a sustained dose related ocular hypotensive effect with no side effects. An increase in eicosanoid and cAMP levels following ICB exposure to MSH indicated their involvement in MSH induced ocular hypotension. MSH and its analogues might have clinical relevance as antiglaucoma drugs with fewer side effects because of their antiallergic and anti-inflammatory properties.