Effect of nesiritide in patients with acute decompensated heart failure

Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.

Understanding morphological variation in the extant koala as a framework for identification of species boundaries in extinct koalas (Phascolarctidae; Marsupialia)

We document morphological variation (both geographical and sexual) in the dentition of the extant koala, Phascolarctos cinereus, in order to facilitate discrimination of species boundaries in extinct phascolarctids. Considerable variation is evident in dental structures previously used to diagnose several phascolarctid fossil species. Consistent patterns of morphological variation are not evident between sexes or geographic regions, with variation as great between samples as within them. Metric variation is evident between the sexes in upper molar dimensions with Victorian (southern) males significantly larger than Victorian females, although this is not reflected in lower molar dimensions or in the Queensland (northern) sample. Male koalas from southern populations generally display significantly larger molars than their northern counterparts; however this trend is not evident in female upper molar dimensions. In both males and females, some, but not all, lower molar dimensions are larger in southern populations than northern. In light of these results, a systematic revision of species of Litokoala suggests L. dicktedfordi' is a junior synonym of L. kutjamarpensis, and the poorly known L. thurmerae is regarded to be a nomen dubium. Further, we describe a partial cranium of a new species of koala from Early Miocene sediments in the Riversleigh World Heritage Area, northern Australia. Litokoala dicksmithi sp. nov. is the fifth koala species recorded from the diverse rainforest assemblages of Riversleigh and the third species referred to the Oligo-Miocene genus Litokoala. Aspects of cranial morphology, including a shortened robust rostrum and broad, irregular nasal aperture, confirm placement of Litokoala as sister taxon to the modern genus Phascolarctos. Relatively large orbits and small body size suggest the possibility that L. dicksmithi was nocturnal, had enhanced visual acuity, and was a more agile arboreal species than the relatively sedentary extant koala

The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments

10.1371/journal.pone.0032460PLoS ONE73e3246

Heart Fatty Acid Binding Protein and cardiac troponin: Development of an optimal rule-out strategy for acute myocardial infarction

10.1186/s12873-016-0089-yBMC Emergency Medicine1613

A Kaupapa Māori approach to a community cohort study of heart disease in New Zealand

Objective: To report the processes and protocols that were developed in the design and implementation of the Hauora Manawa Project, a cohort study of heart disease in New Zealand and to report the participation at baseline. Methods: This study utilised application of a Kaupapa Māori Methodology in gaining tribal and health community engagement, design of the project and random selection of participants from territorial electoral rolls, to obtain three cohorts: rural Māori, urban Māori and urban non-Māori. Logistic regression was used to model response rates. Results: Time invested in gaining tribal and health community engagement assisted in the development and design of clear protocols and processes for the study. Response rates were 57.6%, 48.3% and 57.2%. Co-operation rates (participation among those with whom contact was established) were 74.7%, 66.6% and 71.4%. Conclusions: Use of electoral rolls enables straightforward sampling but results in low response rates because electors have moved. Co-operation rates highlight the acceptability of this research project to the participants; they indicate the strength of Kaupapa Māori Methodologies in engaging Māori participants and community. Implications: This study provides a model for conducting clinical/biomedical research projects that are compatible with cultural protocols and methodologies, in which the primary aim of the research was Māori health gain. Key words: Indigenous population, ethnic groups, cardiology, heart disease

Betaine and trimethylamine-N-oxide as predictors of cardiovascular outcomes show different patterns in diabetes mellitus: An observational study

10.1371/journal.pone.0114969PLoS ONE912e11496

Genomic Risk Variants at 1p13.3, 1q41, and 3q22.3 Are Associated With Subsequent Cardiovascular Outcomes in Healthy Controls and in Established Coronary Artery Genomic Risk Variants at 1p13.3, 1q41, and 3q22.3 Are Associated With Subsequent Cardiovascular Outcomes in Healthy Controls and in Established Coronary Artery Disease

Coronary artery disease (CAD) has multifactorial origins, and although some families are particularly affected, no precise mode of inheritance has been identified. It is likely that this reflects the contribution of numerous genetic components, each conferring a small risk in cumulative interaction with environmental factors to substantively increase disease susceptibility.1 In recent years, significant advances have been made in elucidating the genetic basis of CAD with the completion of several large genome-wide association studies (GWAS) that have looked at the DNA variation across the entire human genome. In a landmark study in 2007, the Wellcome Trust Case Control Consortium identified a region on chromosome 9 (9p21.3) that was the most strongly associated with the risk of developing CAD,2 a finding that has since been replicated in several independent studies.3–6 The 9p21.3 rs1333049 variant is common and may potentially be added to risk profiling in the future. Already it has been reported that adding the 9p21.3 genotype to the traditional risk score significantly improves CAD risk prediction in the community

The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues

10.1371/journal.pone.0039574PLoS ONE76e3957