Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

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Heart failure and preserved left ventricular function: long term clinical outcome.

BACKGROUND: Patients with heart failure (HF) have a poor prognosis. The proportion of patients with HF and preserved left ventricular function (LVF) is increasing. Long term prognosis of HF with preserved LVF may not be so benign. OBJECTIVES: To evaluate the long term clinical outcome of patients with HF and preserved LVF and predictors of outcome. METHODS: We prospectively evaluated 309 patients hospitalized with a definite clinical diagnosis of HF. Patients were followed for a mean of 6.5 years for clinical outcome. RESULTS: More than a third (36%) of the patients had preserved systolic LVF based on echocardiography. The long term survival rate in this group was poor and not significantly different from patients with reduced LVF (28% vs 23% respectively, P=0.2). The adjusted survival rate by Cox regression analysis was also not significantly different (hazard ratio 1.16, 95% confidence interval 0.87-1.55, P=0.31). The event free survival from death or heart failure re-hospitalization was also low in both groups and not significantly different between patients with preserved vs. reduced LVF (12% vs. 10% respectively, P=0.2). Predictors of mortality in patients with preserved LVF were age, functional capacity and serum urea levels. CONCLUSIONS: The long term clinical outcome of patients with heart failure and preserved LVF is poor and not significantly different from patients with reduced LVF

Treatment of Heart Failure Patients with Anxiolytics Is Associated with Adverse Outcomes, with and without Depression

Background: Few studies have evaluated the effect of pharmacologic treatment of anxiety on outcomes in heart failure (HF) patients. This study examined the impact of treatment with anxiolytics on clinical outcomes in a real-world sample of HF patients with and without depression. Methods: Patients diagnosed with HF were retrieved from a large HMO database. Patients prescribed anxiolytic medication and patients diagnosed with depression and/or prescribed anti-depressant medication were followed for cardiac-related hospitalizations and death. Results: The study cohort included 6293 HF patients. Treatment with anxiolytics was associated with decreased one-year survival compared to untreated individuals, with a greater reduction in survival seen in patients diagnosed with depression and/or treated with anti-depressants. Multi-variable analysis adjusting for age, sex, NYHA class, cardiac risk factors and laboratory parameters found that treatment with anxiolytics remained a predictor of mortality even when adjusting for depression. Depression combined with anxiolytic treatment was predictive of increased mortality, and treatment with anxiolytics alone, depression alone and anxiolytic treatment together with depression were each associated with an increased hazard ratio for a composite outcome of death and hospitalization. Conclusions: In this real-world study of HF patients, both treatment with anxiolytics and depression were associated with increased mortality, and anxiolytic therapy remained a predictor of mortality when adjusting for depression. Treatment of anxiety together with depression was associated with the highest risk of mortality. Safe and effective treatment for anxiety and depression is warranted to alleviate the detrimental impact of these disorders on quality and of life and adverse events

Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of pre-existing immunity and surrogate antigen bystander effect

ABSTRACT Oral tolerance is a recognized procedure for induction of antigen-specific peripheral immune hyporesponsiveness. Recently, it has been shown that oral tolerance can be used to prevent experimental colitis. The aim of this study was to test whether induction of oral tolerance toward proteins extracted from inflammatory and noninflammatory colons can alleviate preexisting experimental colitis. Colitis was induced in BALB/c mice by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-induced colitis or normal colons, before, or 7 days after colitis was induced. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon ␥ (IFN␥) and interleukin (IL)4 levels were measured by enzyme-linked immunosorbent assay. Feeding of colitis-or normal colon-extracted proteins before, or following colitis induction, ameliorated colonic inflammation as shown by decreased diarrhea, increased body weight, reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness, and edema. Histological parameters for colitis were markedly improved in tolerized animals, and there was a significant reduction in inflammatory response and mucosal ulcerations. Tolerized mice developed an increase in IL4 and a decrease in IFN␥ serum levels. The results show that induction of oral tolerance to colitis-or normal colon-extracted proteins down-regulated preexisting anticolon immune response, thereby ameliorating experimental colitis. Tolerance induction was mediated via a shift from a proinflammatory T helper (Th)1 to an anti-inflammatory Th2 immune response