Endomyocardial, intralymphocyte, and whole blood concentrations of ciclosporin A in heart transplant recipients.

Background: In the early phases following heart transplantation a main challenge is to reduce the impact of acute rejections. Previous studies indicate that intracellular ciclosporin A (CsA) concentration may be a sensitive acute rejection marker in renal transplant recipients. The aims of this study were to evaluate the relationships between CsA concentrations at different target sites as potential therapeutic drug monitoring (TDM) tools in heart transplant recipients.

EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot).

Aims: The ESC-HF Pilot survey was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). The pilot phase was also specifically aimed at validating structure, performance, and quality of the data set for continuing the survey into a permanent Registry.

Methods: The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 Cardiology Centres in 12 European countries selected to represent the different health systems across Europe.

Influence of crossover on mortality in a randomized study of revascularization in patients with systolic heart failure and coronary artery disease.

Background: To assess the influence of therapy crossovers on treatment comparisons and mortality at 5 years in patients with ischemic heart disease and heart failure randomly assigned to medical therapy alone (MED) or to MED and coronary artery bypass graft (CABG) surgery in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.

Methods And Results: The influence of early crossover (within the first year after randomization) on 5-year mortality was assessed using time-dependent multivariable Cox models. CABG was performed in 65/602 patients (10.

CCL21 is associated with fatal outcomes in chronic heart failure: data from CORONA and GISSI-HF trials.

Aims: Chronic heart failure (HF) is in part characterized by immune activation and inflammation, and factors that regulate lymphocyte trafficking and inflammation may contribute to the progression of this disorder. The homeostatic chemokine CCL21 is a potent regulator of T-cell migration into non-lymphoid tissue and may exert inflammatory properties and influence tissue remodelling. We therefore investigated CCL21 levels and association with fatal outcomes in patients with chronic HF.

Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH.

Background: In several cross-sectional analyses, circulating baseline levels of galectin-3, a protein involved in myocardial fibrosis and remodeling, have been associated with increased risk for morbidity and mortality in patients with heart failure (HF). The importance and clinical use of repeated measurements of galectin-3 have not yet been reported.

Methods And Results: Plasma galectin-3 was measured at baseline and at 3 months in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial (n=1329), and at baseline and at 6 months in patients enrolled in the Coordinating Study Evaluating Outcomes of Advising and Counseling Failure (COACH) trial (n=324).

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan-4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure-overloaded heart.

Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention.

Secreted Wnt modulators in symptomatic aortic stenosis.

Background: Valve calcification and inflammation play key roles in the development of aortic stenosis (AS). The Wnt pathways have been linked to inflammation, bone metabolism, angiogenesis, and heart valve formation. We hypothesized that soluble Wnt modulators may be dysregulated in symptomatic AS.

Soluble glycoprotein 130 predicts fatal outcomes in chronic heart failure: analysis from the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

Background: Glycoprotein 130 (gp130) is the common signal-transducing receptor subunit of the interleukin-6 (IL-6) family, which may be involved in the progression of heart failure (HF). We hypothesized that soluble gp130 would provide prognostic information beyond that of IL-6 in a population with HF from the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

Methods And Results: The associations of soluble gp130 and IL-6 with morbidity, mortality, and mode of death were assessed by immunoassays in a subset of 1452 patients enrolled in the CORONA trial, which included patients with HF, aged ≥60 years, in New York Heart Association classes II to IV, who had ischemic heart disease and a reduced left ventricular ejection fraction.

The predictive value of galectin-3 for mortality and cardiovascular events in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

Background: Galectin-3 is a new biomarker involved in inflammation and fibrogenesis and could therefore contribute to myocardial remodeling. We examined the prognostic value of baseline galectin-3 in a substudy involving approximately 30% of participants in the CORONA study.

Methods: Patients (n = 1462) aged >60 years with systolic, ischemic heart failure (HF) were randomized to 10 mg/d rosuvastatin or placebo.

One year of high-intensity interval training improves exercise capacity, but not left ventricular function in stable heart transplant recipients: a randomised controlled trial.

Background: Heart transplant recipients have lower exercise capacity and impaired cardiac function compared with the normal population. High-intensity interval training (HIIT) improves exercise capacity and cardiac function in patients with heart failure and hypertension, but the effect on cardiac function in stable heart transplant recipients is not known. Thus, we investigated whether HIIT improved cardiac function and exercise capacity in stable heart transplant recipients by use of comprehensive rest- and exercise-echocardiography and cardiopulmonary exercise testing.

Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction.

Background: Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function.

Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial.

In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.

High-intensity interval training improves peak oxygen uptake and muscular exercise capacity in heart transplant recipients.

Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO(2peak) levels of 50-70% predicted value. Our hypothesis was that high-intensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO(2peak.) Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO(2peak) increase.

Heart failure biomarkers: focus on interleukin-1 receptor-like 1-based blood tests.

Heart failure is a leading cause of morbidity and mortality in the Western world. It is often a progressive disease, and the pathophysiology behind this adverse development is not completely understood. Biomarkers are of increasing importance in heart failure research.

Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization.

Objectives: Based on the newly recognized role of the homeostatic chemokines in inflammation, we hypothesized that CXCL13 could modulate atherogenesis and plaque destabilization.

Methods: The study included in vivo analyses in patients with carotid atherosclerosis and in vitro experiments in cells involved in atherogenesis (ie, monocytes/macrophages, vascular smooth muscle cells [SMC], and platelets).

Results: Our main findings were: (i) Patients with carotid atherosclerosis (n = 130) had increased plasma levels of CXCL13 with particularly high levels in symptomatic disease.

Aquaporin-4 in the heart: expression, regulation and functional role in ischemia.

Aquaporins (AQPs) are channel-forming membrane proteins highly permeable to water. AQP4 is found in mammalian hearts; however, its expression sites, regulation and function are largely unknown. The aim was to investigate cardiac AQP4 expression in humans and mice, its regulation by ischemia and hypoxia, and in particular its role in cardiac ischemic injury using AQP4 knockout (KO) mice.

Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials.

Aims: Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF.

Methods And Results: Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF).

Early postoperative left ventricular function by echocardiographic strain is a predictor of 1-year mortality in heart transplant recipients.

Background: Left ventricular (LV) function can be accurately assessed using two-dimensional speckle-tracking echocardiography. The association between reduced LV global longitudinal strain (LVGLS) magnitude and risk for mortality in heart transplant recipients is unclear. The aim of this study was to test the hypothesis that LVGLS could predict 1-year mortality in heart transplant recipients.

Inflammatory cytokines in heart failure: mediators and markers.

Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis of chronic heart failure (HF) contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as tumor necrosis factor (TNF)α, interleukin (IL)-1β and IL-6 in HF patients in plasma and circulating leukocytes, as well as in the failing myocardium itself. There is strong evidence that these mediators are involved in processes leading to cardiac remodeling such as hypertrophy, fibrosis and apoptosis.

Muscular exercise capacity and body fat predict VO(2peak) in heart transplant recipients.

Background: Heart transplant (HTx) recipients usually have reduced exercise capacity, with reported VO2peak levels of 50-70% of predicted values. This study aimed to evaluate central and peripheral factors predictive of VO2peak.

Methods And Results: Fifty-one clinically stable HTx recipients >18 years old and 1-8 years after HTx, underwent maximal exercise testing on a treadmill.

Disturbed carnitine regulation in chronic heart failure--increased plasma levels of palmitoyl-carnitine are associated with poor prognosis.

Background/objectives: Heart failure is characterized by disturbed energy metabolism and impaired mitochondrial function. L-carnitine plays a critical role in fatty acid transport into the mitochondria and may thus influence inflammation and myocardial function. The aim of this study was to investigate carnitine metabolism in relation to progression of heart failure (HF).

Increased levels of inflammatory cytokines and endothelin-1 in alveolar macrophages from patients with chronic heart failure.

Background: Pathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF.

Methodology/principal Findings: Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16).

High-sensitive troponin T and N-terminal-brain-natriuretic-peptide predict outcome in symptomatic aortic stenosis.

Objectives: Aortic stenosis (AS) and atherosclerosis share similarities when it comes to risk factors and disease progression. Like in other heart diseases, we hypothesized that biomarkers like high-sensitive troponin T (hsTnT), N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) and high-sensitive C-reactive protein (hsCRP) could be useful in risk stratification.

Design: A total of 136 patients (57% men, mean age 74 years), referred for evaluation of AS (valve area 0.

Peak oxygen uptake during cardiopulmonary exercise testing determines response to cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy (CRT) is an established treatment modality for advanced heart failure (HF) but 20-30% of patients treated with CRT do not experience clinical improvement. Hence, in this study we aimed to investigate whether baseline cardiopulmonary exercise testing (CPX) can help improve the prediction of a positive functional CRT response.

Methods: This prospective observational study included 76 HF patients undergoing elective CRT implantation and clinical CPX and echocardiographic assessment were performed at baseline, 6, and 12 months.