Clinical characteristics and prognosis of patients with heart failure and high concentrations of interleukin-17D.

AIMS: Heart failure (HF) is associated with cytokine activation and inflammation. Experimental evidence suggests that plasma interleukin-17 (IL-17) is associated with myocardial fibrosis and cardiac dysfunction in HF. IL-17D, a subtype of IL-17 originates from particular tissues such as the heart. However, there is very limited data on the IL-17 cytokine family in patients with HF. Therefore, we investigated the association between circulating IL-17D levels, clinical characteristics and outcome in a large cohort of patients with heart failure. METHODS AND RESULTS: Plasma IL-17D was measured in 2032 patients with HF from 11 European countries using a proximity extension assay. The primary outcome was a composite of HF hospitalization or all-cause mortality. Patients with higher plasma IL-17D concentrations were more likely to have atrial fibrillation (AF), renal dysfunction and heart failure with preserved ejection fraction (HFpEF) and had higher plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations (all p < 0.001). IL-17D was not associated with interleukin-6 (IL-6) or C-reactive protein (CRP) concentrations. After adjustment for confounders in a multivariable Cox regression analysis, patients in the highest quartile of plasma IL-17D had a significantly increased risk of the composite outcome of HF hospitalization or all-cause mortality compared to patients in the lowest quartile [Hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57]. CONCLUSION: In patients with HF, elevated plasma IL-17D concentrations are associated with higher plasma NT-proBNP concentrations and a higher prevalence of AF and renal dysfunction. High IL-17D concentrations are independently associated with worse outcome.

Immunomodulation and immunopharmacology in heart failure.

The immune system is intimately involved in the pathophysiology of heart failure. However, it is currently underused as a therapeutic target in the clinical setting. Moreover, the development of novel immunomodulatory therapies and their investigation for the treatment of patients with heart failure are hampered by the fact that currently used, evidence-based treatments for heart failure exert multiple immunomodulatory effects. In this Review, we discuss current knowledge on how evidence-based treatments for heart failure affect the immune system in addition to their primary mechanism of action, both to inform practising physicians about these pleiotropic actions and to create a framework for the development and application of future immunomodulatory therapies. We also delineate which subpopulations of patients with heart failure might benefit from immunomodulatory treatments. Furthermore, we summarize completed and ongoing clinical trials that assess immunomodulatory treatments in heart failure and present several therapeutic targets that could be investigated in the future. Lastly, we provide future directions to leverage the immunomodulatory potential of existing treatments and to foster the investigation of novel immunomodulatory therapeutics.

Heart failure with normal LVEF in BIOSTAT-CHF.

AIMS: Several studies have shown that heart failure (HF) drug treatment seems to benefit patients with preserved ejection fraction (HFpEF) and a left ventricular ejection fraction (LVEF) up to 55-60% but not with higher LVEF. Certain HF drugs are now indicated in patients with HFpEF and a LVEF below normal. However, not much is known about patients with a normal LVEF. Therefore, we investigated the prevalence, clinical characteristics and outcome of patients with HF and a normal LVEF. METHODS AND RESULTS: Normal LVEF was defined according to the Recommendations for Cardiac Chamber Quantification from the American Society of Echocardiography as a LVEF ≥62% for men and ≥ 64% for women. Preserved ejection fraction was defined as a LVEF ≥50% and reduced ejection fraction as a LVEF <50%. In the total cohort of 1568 studied patients with heart failure (mean age 73 years; 33.6% female) 57 patients (3.6%) had a normal LVEF. These patients least likely had a previous myocardial infarction (p < 0.001) or diabetes (p = 0.045), had the lowest Left Ventricular End Diastolic Diameter (p < 0.001), the highest rate of previous HF hospitalization in the last year (p = 0.015), the highest cardiac output (p < 0.001) and were most frequently women (p < 0.001). Patients with a normal LVEF had the lowest risk for the primary combined outcome of all-cause mortality and HF hospitalization. CONCLUSION: Only 3.6% of patients with HF had a sex-adjusted normal LVEF. Despite the sex-adjusted cut-offs they were more frequently female with less ischemic heart disease, higher cardiac output and better clinical outcomes.