Novel therapies for heart failure: focus on anti-inflammatory strategies

The understanding of the pathomechanisms leading to heart failure has evolved from the simplistic pump-failure concept to the more complex syndrome involving neurohormonal and inflammatory systems. Anti-inflammatory therapy targeting specific cytokines, however, such as tumor necrosis factor-alpha, has failed to show clinical benefit. As a result, the focus has turned toward more broad-spectrum anti-inflammatory strategies. This review examines the various broad-spectrum anti-inflammatory modalities that have been used in heart failure: IV immunoglobulin administration, immune modulation therapy, immune adsorption, and plasmapheresis.     

Worsening renal function is not associated with response to treatment in acute heart failure

Background

About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality.

Methods

We performed retrospective chart review of patients admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN) values measured both on admission and discharge. Survival analysis was conducted using Cox proportional hazards model and correlation was measured using Spearman's rank correlation test.

Results

358 patients admitted for ADHF were evaluated. WRF was defined as > 20% reduction in eGFR from admission to discharge and response to treatment was assessed by ΔBNP. There was a statistically significant reduction in BNP and increase in BUN during the admission. ΔBNP did not correlate with either ΔGFR or ΔBUN. Patients who developed WRF and those who did not, had a similar reduction in BNP. On univariate survival analysis, ΔBUN, but not ΔeGFR, was associated with 1-year mortality. In multivariate Cox proportional hazards model, BUN at discharge was associated with 1-year mortality (HR: 1.02, p < 0.001), but ΔeGFR and ΔBUN were not associated with the primary endpoint.

Conclusion

During ADHF treatment, ΔBNP was not associated with changes in renal function. Development of WRF during ADHF treatment was not associated with mortality. Our study suggests that development of WRF should not preclude diuresis in ADHF patients in the absence of volume depletion.     

Quality of Life Impacts of Bright Light Treatment,Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial

Objective:Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome.Methods:This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression.Results:Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores.Conclusion:The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.     

Validation of guinea pig model of allergic rhinitis by oral and topical drugs

Ovalbumin-induced guinea pig model of rhinitis was assessed for its utility in the studies of rhinitis. Systemic sensitization and challenge with ovalbumin-induced rhinitis symptoms and an increase in anti-OVA-IgE and IgG titers, positive skin reactions and nasal lavage IL-4 concentration. Histopathology of nasal mucosa showed infiltration of eosinophils and other inflammatory cells consistent with the symptoms. Topical sensitization of ovalbumin yielded inconsistent symptoms of rhinitis. In systemic sensitization model, repeated challenge of ovalbumin caused similar response for at least 3 consecutive challenges. The symptoms were affected by relative humidity in the air and dosing volume of topical drugs. Sneezing and lacrimation were reduced by acute oral administration of the H1 receptor antagonists and steroids or the prophylactic oral administration of cysteinyl leukotriene (CysLT1) receptor antagonist montelukast or acute topical antihistamines, mast cell stabilizer sodium cromoglycate and anticholinergic agent ipratropium bromide, but not by a topical steroid. Nose rubbing was reduced significantly by some oral and topical antihistamines. Oral steroids offered excellent protection against all symptoms. Dexamethasone and montelukast also inhibited nasal lavage IL-4 concentration and inflammatory cell infiltration. Treatment with topical steroid fluticasone for 2 weeks had no effect on sneezing or rubbing. However, it caused complete inhibition of congestion. The cyclooxygenase inhibitor indomethacin had no effect on symptoms of rhinitis. The adrenergic alpha receptor agonist-decongestant oxymetazoline caused reduction in congestion. These results suggest that differential responsiveness to symptoms of rhinitis by a new agent can be very well profiled in the model in congruence with the mediation pathways and mechanism of action of drugs. The model provides complete symptomatic characterization of rhinitis and is a good tool for its study.     

Therapy for prevention of post-stroke depression

INTRODUCTION: Depression is the most common psychiatric disorder after stroke that adversely affects stroke outcomes. It is often underdiagnosed and inadequately treated. Hence, there is growing interest in interventions to prevent depression in stroke patients, which is in concert with emerging data that indicate prevention of major depression in selective high-risk populations may be effective. AREAS COVERED: This article reviews the state of the current literature on pharmacologic and psychosocial preventive intervention strategies for depression in stroke patients. EXPERT OPINION: The emerging data indicate that antidepressants and psychological therapies may be effective and safe in preventing post-stroke depression. More well-designed preventive trials are required to determine the efficacy and cost-effectiveness of preventive interventions targeting stroke patients, who are a high-risk group for depression.