Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins.

Background Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation. Methods and results Whole blood from 32 CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-α) release was quantified. Reference standard endotoxin at concentrat…

Exercise hyperventilation in chronic heart failure is not caused by systemic lactic acidosis

Background: Patients with heart failure have an abnormally high ventilatory response to exercise associated with gas exchange defects and reduced arterial pCO2. Aims: We examined the possibility of lactic acidosis as the stimulus to this increased ventilation that abnormally depresses pCO2 during exercise in heart failure. Method and results: We studied 18 patients with chronic heart failure. We measured VE/VCO2 slope during exercise, arterial blood gases and lactate concentrations during cardiopulmonary exercise testing (rest, peak exercise and one minute after the end of exercise). Neither VE/VCO2 slope nor arterial pCO2 were related to arterial lactate concentrations at peak exercise (r=…

Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure.

Bacterial endotoxin activity is elevated in patients with decompensated chronic heart failure (HF) and acts as a potent stimulus for immune activation. We sought to determine whether endotoxin, at an activity level seen in vivo (around 0.6 EU/ml), is sufficient to stimulate the secretion of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha soluble receptor (sTNFR2) in ex vivo whole blood from patients with HF. We studied 15 patients with HF (aged 65 +/- 1.9 years, New York Heart Association class 2.1 +/- 0.3, left ventricular ejection fraction 31 +/- 5%; mean +/- SEM), of whom 5 had cardiac cachexia, and 7 healthy control subjects (59 +/- 5 years, p = NS). Reference endotoxin was added …

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

Background: Retrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown. Objectives: We investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF. Methods: Through the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HFLT), 4,438 outpatients were identified and classified into: reduced (= 50% HFpEF) LVEF. Endpoints were t…

Differential contribution of dead space ventilation and low arterial pCO2 to exercise hyperpnea in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In chronic heart failure (CHF), the abnormally large ventilatory response to exercise (VE/VCO(2) slope) has 2 conceptual elements: the requirement of restraining arterial partial pressure of carbon dioxide (pCO(2)) from increasing (because of an increased ratio between increased physiologic dead space and tidal volume [VD/VT]) and the depression of arterial pCO(2) by further increased ventilation, which necessarily implies an important non-carbon dioxide stimulus to ventilation. We aimed to assess the contribution of these 2 factors in determining the elevated VE/VCO(2) slope in CHF. Thirty patients with CHF underwent cardiopulmonary exercise testing (age 65 +/- 11 years, left ventricular e…

Measuring physical activity with activity monitors in patients with heart failure: from literature to practice. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology

The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activi…

Treatment of Chronic Congestive Heart Failure

The Peptide for Life Initiative: a call for action to provide equal access to the use of natriuretic peptides in the diagnosis of acute heart failure across Europe

n/a Funding Agencies|Applied Therapeutics; Innolife; Novartis PharmaceuticalsNovartis; Abbott DiagnosticsAbbott Laboratories; AstraZenecaAstraZeneca; AbbottAbbott Laboratories; Boehringer IngelheimBoehringer Ingelheim; Cardior Pharmaceuticals Gmbh; Ionis Pharmaceuticals, Inc.; Novo NordiskNovo Nordisk; RocheRoche Holding; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission; Swiss Heart Foundation; KTI; European UnionEuropean Commission; University of Basel; University Hospital Basel; Beckman Coulter; BRAHMS; Idorsia; NovartisNovartis; Ortho Clinical Diagnostics; Quidel; SiemensSiemens AG; Singulex; Sphingotec; CardioRenal

Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival

Heat shock protein 70 (Hsp70) is essential for cellular recovery, survival and maintenance of cellular function. Research into the possible use of Hsp70 as a cytoprotective therapeutic agent is ongoing. Chronic heart failure (CHF) is a state associated with systemic inflammation, particularly in patients with cardiac cachexia. We hypothesised that circulating Hsp70 levels are elevated in patients with CHF, more so in cachechtic patients, and that Hsp70 levels would relate to mortality.We studied 107 patients (28 female, age 67+/-1 years, NYHA class 2.6+/-0.6 and LVEF 29+/-1%, mean+/-SEM) and 21 controls. Cardiac cachexia was present in 32 patients. Hsp70 was detectable in 41% of CHF patient…

The relationship between age and production of tumour necrosis factor-α in healthy volunteers and patients with chronic heart failure

Ageing is associated with an altered immune response. Elevated plasma levels of tumour necrosis factor-alpha (TNF-alpha) are present in patients with advanced chronic heart failure (CHF). However, the relationship between age and the immune response in CHF is unknown.We investigated the relationship between age and the TNF-alpha generating capacity of lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in nine healthy control subjects (mean age 51.6+/-3.6 years, age range 39-75 years) and 22 stable patients with CHF (mean age 68.3+/-1.5 years, age range 52-78 years, NYHA class 3.0+/-0.2). We also tested the TNF-alpha generating capacity of all control subjects and …

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health profe…

The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure

Background: Activation of the endotoxin (LPS) receptor, CD14, leads to tumor necrosis factor-alpha (TNF) production. Plasma LPS activity is elevated in patients with severe chronic heart failure (CHF). An anti-CD14 antibody, IC14, blocks TNF production in healthy volunteers. It is not known whether IC14 prevents TNF production in CHF patients. Methods and results: Blood from 20 CHF patients (age 64±2.1 years, NYHA class 2.2±0.1, LVEF 27±3%, mean±SEM) was pre-incubated with 0.5, 1.0, 5.0, 10 and 50 μg/mL IC14 for 1 h followed by incubation with 1 or 10 ng/mL LPS for 6 h. Fourteen subjects served as controls (58±2.4 years). LPS-stimulated TNF release was 76% and 60% greater at 1 and 10 ng/mL …