Serum thyroid-stimulating hormone levels are not associated with exercise capacity and lung function parameters in two population-based studies.

Background: Thyroid dysfunction has been described to be linked to a variety of cardiovascular morbidities. Through this pathway thyroid function might also be associated with cardiorespiratory function and exercise capacity. So far only few patient-studies with small study populations investigated the association between thyroid dysfunction and exercise capacity.

Sphingosine-1-phosphate induces thrombin receptor PAR-4 expression to enhance cell migration and COX-2 formation in human monocytes.

Thrombin is not only a central factor in blood coagulation but also stimulates inflammatory processes, including monocyte responses, via activation of PARs. The signaling lipid S1P is a major determinant of monocyte function. Here, we established an interaction between S1P and human monocyte responses to thrombin.

Glycated hemoglobin as a marker of subclinical atherosclerosis and cardiac remodeling among non-diabetic adults from the general population.

Background: Elevated glycated hemoglobin (HbA1c) is associated with increased risk of cardiovascular disease (CVD) and mortality but little is known about potential mechanisms underlying the reported associations.

Methods: We used data from 1798 non-diabetic participants from the population-based cohort Study of Health in Pomerania (SHIP) to investigate cross-sectional and longitudinal associations of HbA1c with subclinical atherosclerosis (common carotid artery intima-media thickness [CCA-IMT]), cardiac structure (left ventricular mass [LVM]), and cardiac function (fractional shortening).

Results: Cross-sectional analyses revealed a positive association between HbA1c and mean CCA-IMT with a 0.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization.

Stiffness of left ventricular cardiac fibroblasts is associated with ventricular dilation in patients with recent-onset nonischemic and nonvalvular cardiomyopathy.

Background: Ventricular dilation is known as a pivotal predictor in recent-onset cardiomyopathy (ROCM), but its pathophysiology is not fully understood. In the present study we investigated whether single-cell stiffness of right and left ventricular-derived fibroblasts has an effect on cardiac phenotype in patients with ROCM.

Methods And Results: Patients with endomyocardial biopsy-proven ROCM were included (n=10).

Cohort profile: Greifswald approach to individualized medicine (GANI_MED).

Background: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine.

Molecular phenotypes of human parvovirus B19 in patients with myocarditis.

Aim: To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM).

Methods: Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.

A novel flow-based parameter of collateral function assessed by intracoronary thermodilution.

Background: Currently, many methods for quantitation of coronary collateral function are based on intracoronary pressure measurements distal of an occluded balloon, which do not fully account for the dynamic nature of collateral flow. Therefore, a flow-based parameter of coronary collateral function based upon principles of thermodilution was evaluated.

Methods: In 26 patients with a high-grade coronary artery stenosis, intracoronary hemodynamics were analyzed by the RadiAnalyzer system (St Jude Medical), including fractional flow reserve (FFR), index of microcirculatory resistance (IMR), and the pressure-based collateral flow index (CFI) during balloon occlusion and hyperemia (intravenous adenosine).

Efficacy of a minicourse in radiation-reducing techniques in invasive cardiology: a multicenter field study.

Objectives: Our goal was to validate an educational 90-min minicourse in lower-irradiating cardiac invasive techniques.

Background: Despite comprehensive radiation safety programs, patient radiation exposure in invasive cardiology remains considerable.

Methods: Before and at a median period of 3.

Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.

Objectives: This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.

Background: AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.

Antibodies against potassium channel interacting protein 2 induce necrosis in isolated rat cardiomyocytes.

Auto-antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti-KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood.

Do patients with type 1 and type 2 diabetes really have an impaired endothelial function? A population-based propensity score matching analysis.

Background: Previous studies suggested an impaired endothelial function in patients with diabetes. However, the validity of this finding may be limited by the lack of adequate adjustment for further cardiovascular confounders. We assessed endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in patients with either type 1 or type 2 diabetes in comparison with non-diabetic controls.

New stent surface materials: the impact of polymer-dependent interactions of human endothelial cells, smooth muscle cells, and platelets.

Despite the development of new coronary stent technologies, in-stent restenosis and stent thrombosis are still clinically relevant. Interactions of blood and tissue cells with the implanted material may represent an important cause of these side effects. We hypothesize material-dependent interaction of blood and tissue cells.

A new, accurate predictive model for incident hypertension.

Objective: Data mining represents an alternative approach to identify new predictors of multifactorial diseases. This work aimed at building an accurate predictive model for incident hypertension using data mining procedures.

Methods: The primary study population consisted of 1605 normotensive individuals aged 20-79 years with 5-year follow-up from the population-based study, that is the Study of Health in Pomerania (SHIP).

Site-selective immobilization of anti-CD34 antibodies to poly(l-lactide) for endovascular implant surfaces.

Aiming at a speed up of the re-endothelialization process of biodegradable endovascular implants, novel approaches for the functionalization of poly(l-lactide) (PLLA) with anti-CD34 antibodies were established. We propose a three-step process involving PLLA surface activation with functional amino groups, attachment of a protein repelling peptide spacer, and covalent random or site-selective immobilization of the antibodies. Obtainable antibody surface densities and antigen binding capacities were thoroughly evaluated by means of enzyme-linked immunosorbent assay.

A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.

Aims: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM.

Pulmonary hypertension in patients with idiopathic pulmonary fibrosis - the predictive value of exercise capacity and gas exchange efficiency.

Exercise capacity and survival of patients with IPF is potentially impaired by pulmonary hypertension. This study aims to investigate diagnostic and prognostic properties of gas exchange during exercise and lung function in IPF patients with or without pulmonary hypertension. In a multicentre setting, patients with IPF underwent right heart catheterization, cardiopulmonary exercise and lung function testing during their initial evaluation.

Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.

In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.

Proteomic analyses of age related changes in A.BY/SnJ mouse hearts.

Background: A.BY/SnJ mice are used to study pathological alterations in the heart due to enteroviral infections. Since age is a well-known factor influencing the susceptibility of mice to infection, response to stress and manifestation of cardiovascular diseases, the myocardial proteome of A.

Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study.

Background: Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction.

Methods And Results: Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.

Effects of smoking on arterial distensibility, central aortic pressures and left ventricular mass.

Background: The effects of smoking on central aortic pressures and the age-related increase in left ventricular mass (LVM) are largely unknown. We studied the relationship between smoking, arterial distensibility, central aortic pressures and left ventricular mass in two population-based studies.

Methods: Data was obtained from two German population-based studies (KORA and SHIP, participants' ages 25-84 years).

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death.

Personalized cardiovascular medicine: concepts and methodological considerations.

The primary goals of personalized medicine are to optimize diagnostic and treatment strategies by tailoring them to the specific characteristics of an individual patient. In this Review, we summarize basic concepts and methods of personalizing cardiovascular medicine. In-depth characterization of study participants and patients in general practice using standardized methods is a pivotal component of study design in personalized medicine.