Malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an ACAP-HF data analysis

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 × serum albumin, g/dL) + {41.7 × present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS

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.

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Medication dosing for heart failure with reduced ejection fraction — opportunities and challenges

Multiple drug classes have shown incremental benefits in heart failure with reduced ejection fraction. Most of these trials were designed to achieve specific doses of the investigational agent. Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated. However, with the increasing number of available therapies, clinicians face the challenge of simultaneously using several drugs, achieving target doses, and managing side effects that are often overlapping. Blood pressure, renal function, hyperkalaemia, and other factors may impede achieving target doses of all medications, leaving clinicians with dilemmas as to how to sequence and dose these various classes of drugs. The guideline-directed eligibility for certain drugs and devices requires stability on maximally tolerated doses of background therapies. However, significant variability exists in dosing achieved in clinical practice. We discuss the existing background data regarding the doses of heart failure medications in clinical trials and in practice, and provide recommendations on how to navigate this complex therapeutic decision-making. © 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiolog

Discontinuation and non-publication of heart failure randomized controlled trials: a call to publish all trial results

Aims: Discontinuation or non-publication of trials may hinder scientific progress and violates the commitment made to research participants. We sought to identify the prevalence of discontinuation and non-publication of heart failure (HF) clinical trials. Methods and results: We conducted a cross-sectional search of ClinicalTrials.gov to identify all completed and discontinued HF clinical trials. We limited our search to only include trials that were completed by 31 December 2017. Trials were investigated to identify reasons for discontinuation. Informative termination was defined as trial termination due to safety or efficacy concerns. Data pertaining to the trial phase, funding, intervention, enrolment, and trial completion date were extracted for each trial. A total of 572 trials were included. Of these, 21% (n = 118) were discontinued before completion. Patient accrual was the most frequently cited reason (n = 42; 36%) for trial discontinuation, followed by informative termination (n = 16; 14%) and funding (n = 14; 12%). Overall, 24 780 patients were enrolled in trials that were terminated. Of trials that were completed and not terminated, nearly one-third (n = 131/454; 29%) were not published. Seventy-nine (24%) trials were published within 12 months, 192 (59%) within 24 months, and 252 (78%) trials within 36 months. Conclusions: Discontinuation and non-publication of HF trials is common. This raises ethical concerns towards participants who volunteer for research and are exposed to potential risks, inconvenience, and discomfort without furthering scientific progress. © 2020 The Authors. ESC Heart Failure published by John Wiley &amp; Sons Ltd on behalf of European Society of Cardiolog

In-hospital worsening heart failure

Acute worsening heart failure (WHF) is seen in a sizable portion of patients hospitalized for heart failure, and is increasingly being recognized as an entity that is associated with an adverse in-hospital course. WHF is generally defined as worsening heart failure symptoms and signs requiring an intensification of therapy, and is reported to be seen in anywhere from 5% to 42% of heart failure admissions. It is difficult to ascertain the exact epidemiology of WHF due to varying definitions used in the literature. Studies indicate that WHF cannot be precisely predicted on the basis of baseline variables assessed at the time of admission. Recent data suggest that some experimental therapies may reduce the risk of development of WHF among hospitalized heart failure patients, and this is associated with a reduction in risk of subsequent post-discharge cardiovascular mortality. In this respect, WHF holds promise as a endpoint for acute heart failure clinical trials to better elucidate the benefit of targeted novel therapies. Better understanding of the pathophysiology and a consensus on the definition of WHF will further improve our epidemiological and clinical understanding of this entity. © 2015 The Authors. © 2015 European Society of Cardiology

Contemporary Epidemiology, Management, and Outcomes of Patients Hospitalized for Heart Failure in China: Results From the China Heart Failure (China-HF) Registry

Background Contemporary data on the epidemiology of heart failure (HF) in China are scarce. The China-HF Registry was designed to investigate clinical characteristics, management, and outcomes of patients hospitalized for HF in China. Methods and Results Data were collected prospectively on 13,687 patients with a primary discharge diagnosis of HF who were enrolled from 132 participating hospitals from January 2012 to September 2015. Data from the China-HF Registry was compared with previously published literature. The mean age was 65 ± 15 years, 59.1% were male, and 36.0% had preserved ejection fraction. Age, body mass index, and systolic blood pressure were lower than in high-income countries. Common comorbidities included hypertension (50.9%), coronary heart disease (49.6%), and atrial fibrillation (24.4%). The overall use of diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), and β-blockers at admission was 30.1%, 27.0%, and 25.6%, respectively, which was lower than in other registries. For patients discharged alive, ACEI/ARB, β-blocker, and mineralocorticoid receptor antagonist use in patients with reduced ejection fraction was 67.5%, 70.0%, and 74.1%, respectively; device use was much lower. The median length of hospital stay was 10 (range 7–15) days, and in-hospital mortality was 4.1 ± 0.3%. Predictors of mortality included low systolic blood pressure, acute myocardial infarction, infection, right bundle branch block, and elevated total bilirubin and blood urea nitrogen level. Conclusions Several important findings in patient profile and treatment patterns among Chinese patients with HF were noted compared with published literature. These data underscore the need for regional characterization of HF for global clinical trials and for the identification of several quality improvement opportunities. © 2017 Elsevier Inc

Calogênese, embriogênese somática e isolamento de protoplastos em variedades de laranja doce Callus induction, somatic embryogenesis and protoplast isolation from sweet orange varieties

Com o objetivo de produzir calos embriogênicos de citros, óvulos abortados de frutos maduros de 6 variedades de laranja doce (Citrus sinensis L. Osbeck), ‘Bahia Cabula’, ‘Baianinha’, ‘Hamlin’, ‘Orvalho de Mel’, ‘Rubi’ e ‘Valência’ foram introduzidos em meio de cultivo MT modificado com adição de extrato de malte, com e sem adição de 5 mg L-1 benziladenina (BA). Os calos obtidos das variedades ‘Bahia Cabula’, ‘Orvalho de Mel’, ‘Rubi’ e ‘Valência’ foram cultivados em meio basal MT, contendo os carboidratos maltose, galactose, lactose, glicose ou sacarose nas concentrações de 18; 37; 75; 110 e 150 mM para a indução da embriogênese somática. Os calos destas mesmas variedades foram submetidos ao isolamento de protoplastos, com o uso de 3 soluções enzimáticas. Os resultados revelaram que há influência do genótipo sobre a calogênese. A embriogênese somática foi estimulada na presença de galactose, para a maioria das variedades. A solução enzimática composta de 1% de celulase, 1% de macerase e 0,2% de pectoliase foi a mais adequada para o isolamento de protoplastos a partir de calos das variedades de laranja doce estudadas.<br>Intending to produce embryogenic citrus calli (Citrus sinensis L. Osbeck), aborted ovules of ripe fruits from six sweet orange varieties (‘Bahia Cabula’, ‘Baianinha’, ‘Hamlin’, ‘Orvalho de Mel’, ‘Rubi’ and ‘Valencia’) were introduced onto modified MT medium with and without benzyladenine (BA). Calli obtained from ‘Bahia Cabula’, ‘Orvalho de Mel’, ‘Rubi’ and ‘Valencia’ varieties were grown on MT basal medium modified with the carbohydrates maltose, galactose, lactose, glucose and sucrose at 18; 37; 75; 110 and 150 mM. The effect on somatic embryogenesis was studied. Calli from the same genotypes were submitted to protoplast isolation, using three different enzymatic solutions. Results revealed the genotype effect in the callus induction. Somatic embryogenesis was stimulated in the presence of galactose, for most varieties. Enzymatic solution composed of 1% cellulase, 1% macerase and 0,2% pectolyase was the best for protoplast isolation from calli of all genotypes tested