The value of clinical routine blood biomarkers in predicting long-term mortality after stroke.

Background: Several blood biomarkers have been identified as predictors for poor outcome after ischemic stroke. However, recent studies mainly focused on single or experimental biomarkers and considered rather short follow-up intervals limiting their value for daily clinical practice. We, therefore, aimed to compare various clinical routine blood biomarkers for their predictive value on post-stroke mortality over a 5-year follow-up period.

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.

Background: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial.

Methods: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling.

Liver Fibrosis-4 index indicates atrial fibrillation in acute ischemic stroke.

Background: Non-alcoholic fatty liver disease and particularly liver fibrosis are related to cardiovascular disease and may indicate an increased risk for atrial fibrillation (AF), but this association has not yet been systematically investigated in a cohort of ischemic stroke patients.

Methods: We analyzed data from a prospective single-center study enrolling all consecutive ischemic stroke patients admitted to our stroke unit over a 1-year period. All patients received a thorough etiological workup.

Predicting atrial fibrillation after cryptogenic stroke via a clinical risk score-a prospective observational study.

Background And Purpose: Atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long-term rhythm monitoring. There is an unmet need for a pre-selection of CS patients benefitting from such work-up. A clinical risk score was therefore developed for the prediction of AF after CS and its performance was evaluated over 1 year of follow-up.

Impact of electric cardioversion on platelet activation.

Introduction: Atrial fibrillation (AF) comes along with high risk of stroke. This risk continues even after re-establishing sinus rhythm with cardioversion. Aim of this study is to evaluate the contribution of electric cardioversion (EC) to platelet activation and procoagulatory tendency.

No antiarrhythmic effect of direct oral anticoagulants versus vitamin K antagonists in paroxysmal atrial fibrillation patients undergoing catheter ablation.

Introduction: Direct oral anticoagulants (DOACs) are superior to vitamin K antagonists (VKAs) for the prevention of stroke in atrial fibrillation (AF) patients with elevated stroke risk. Possible antiarrhythmic effects of DOACs have been discussed. We analyzed impact of DOAC treatment on recurrence-free survival after AF catheter ablation.

The role of stretch, tachycardia and sodium-calcium exchanger in induction of early cardiac remodelling.

Stretch and tachycardia are common triggers for cardiac remodelling in various conditions, but a comparative characterization of their role in the excitation-transcription coupling (ETC) and early regulation of gene expression and structural changes is lacking. Here, we show that stretch and tachycardia directly induced hypertrophy of neonatal rat cardiac myocytes and also of non-myocytes. Both triggers induced similar patterns of hypertrophy but had largely distinct gene expression profiles.

Wearable cardioverter-defibrillator as bridging to ICD in pediatric hypertrophic cardiomyopathy with myocardial bridging - a case report.

Background: There is only limited experience with wearable cardioverter-defibrillators (WCD) in pediatric patients. We report on the successful application of a WCD in an adolescent patient with hypertrophic cardiomyopathy and myocardial bridging.

Case Presentation: A 15-year-old girl presented with a history of recurrent syncope, dyspnea, and vertigo with exercise.

Blood Biomarkers of Heart Failure and Hypercoagulation to Identify Atrial Fibrillation-Related Stroke.

Background and Purpose- Occult atrial fibrillation (AF) causes a relevant proportion of initially cryptogenic stroke (CS), but prolonged rhythm monitoring is difficult to apply to all such patients. We hypothesized that blood biomarkers indicating heart failure (NT-proBNP [N-terminal pro-brain natriuretic peptide]) and hypercoagulability (D-dimer, AT-III [antithrombin-III]) were associated with AF-related stroke and could serve to predict the likelihood of AF detection in CS patients early on. Methods- Over a 1-year period, we prospectively applied a defined etiologic work-up to all ischemic stroke patients admitted to our stroke unit.

Is there a difference in rhythm outcome between patients undergoing first line versus second line paroxysmal atrial fibrillation ablation?

Background: Catheter ablation of atrial fibrillation (AF) is an established second line therapy for patients with symptomatic paroxysmal AF (PAF) and may be considered as a first line therapy in selected patients who are highly symptomatic, considering patient choice, benefit, and risk, according to recent guidelines. Our study investigated whether a first line vs. second line ablation approach may result in improved sinus rhythm maintenance after ablation.

Crosstalk between FGF23- and angiotensin II-mediated Ca signaling in pathological cardiac hypertrophy.

Heart failure (HF) manifestation and progression are driven by systemic activation of neuroendocrine signaling cascades, such as the renin-angiotensin aldosterone system (RAAS). Fibroblast growth factor 23 (FGF23), an endocrine hormone, is linked to HF and cardiovascular mortality. It is also a mediator of left-ventricular hypertrophy (LVH).

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function.

Background: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.

Methods: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium).

Targeting cardiac hypertrophy: toward a causal heart failure therapy.

Cardiac hypertrophy is commonly observed in conditions of increased hemodynamic or metabolic stress. This hypertrophy is not compensatory but rather reflects activation of maladaptive cellular processes that promote disease progression. Myocardial hypertrophy serves as a diagnostic and prognostic marker of cardiac remodeling, and underlying regulatory processes have provided effective therapeutic targets to slow disease progression and improve outcome.

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.

Importance: Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal.

Objective: To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs.

Early remodeling of perinuclear Ca2+ stores and nucleoplasmic Ca2+ signaling during the development of hypertrophy and heart failure.

Background: A hallmark of heart failure is impaired cytoplasmic Ca(2+) handling of cardiomyocytes. It remains unknown whether specific alterations in nuclear Ca(2+) handling via altered excitation-transcription coupling contribute to the development and progression of heart failure.

Methods And Results: Using tissue and isolated cardiomyocytes from nonfailing and failing human hearts, as well as mouse and rabbit models of hypertrophy and heart failure, we provide compelling evidence for structural and functional changes of the nuclear envelope and nuclear Ca(2+) handling in cardiomyocytes as remodeling progresses.

Subclinical abnormalities in sarcoplasmic reticulum Ca(2+) release promote eccentric myocardial remodeling and pump failure death in response to pressure overload.

Objectives: This study sought to explore whether subclinical alterations of sarcoplasmic reticulum (SR) Ca(2+) release through cardiac ryanodine receptors (RyR2) aggravate cardiac remodeling in mice carrying a human RyR2(R4496C+/-) gain-of-function mutation in response to pressure overload.

Background: RyR2 dysfunction causes increased diastolic SR Ca(2+) release associated with arrhythmias and contractile dysfunction in inherited and acquired cardiac diseases, such as catecholaminergic polymorphic ventricular tachycardia and heart failure (HF).

Methods: Functional and structural properties of wild-type and catecholaminergic polymorphic ventricular tachycardia-associated RyR2(R4496C+/-) hearts were characterized under conditions of pressure overload induced by transverse aortic constriction (TAC).

Spongious hypertrophic cardiomyopathy in patients with mutations in the four-and-a-half LIM domain 1 gene.

Background: X-linked myopathy with postural muscle atrophy is a novel X-linked myopathy caused by mutations in the four-and-a-half LIM domain 1 gene (FHL1). Cardiac involvement was suspected in initial publications. We now systematically analyzed the association of the FHL1 genotype with the cardiac phenotype to establish a potential cardiac involvement in the disease.

Transcription factor GATA4 is activated but not required for insulin-like growth factor 1 (IGF1)-induced cardiac hypertrophy.

Insulin-like growth factor 1 (IGF1) promotes a physiological type of cardiac hypertrophy and has therapeutic effects in heart disease. Here, we report the relationship of IGF1 to GATA4, an essential transcription factor in cardiac hypertrophy and cell survival. In cultured neonatal rat ventricular myocytes, we compared the responses to IGF1 (10 nmol/liter) and phenylephrine (PE, 20 μmol/liter), a known GATA4 activator, in concentrations promoting a similar extent of hypertrophy.

CMV promoter is inadequate for expression of mutant human RyR2 in transgenic rabbits.

Introduction: Fundamental differences in Ca²+ homeostasis between mice and larger mammals require the validation of the mechanisms of arrhythmogenesis before translation into human pathophysiology. The purpose of this study was to create transgenic rabbits that express defective human cardiac ryanodine receptor (hRyR2) with a mutation (R4497C) causing a clinically relevant arrhythmogenic syndrome.

Methods: The construct pcDNA3-EGFP-hRyR2-R4497C with the CMV promoter was used to generate transgenic rabbits.

Heart failure-associated changes in RNA splicing of sarcomere genes.

Background: Alternative mRNA splicing is an important mechanism for regulation of gene expression. Altered mRNA splicing occurs in association with several types of cancer, and a small number of disease-associated changes in splicing have been reported in heart disease. However, genome-wide approaches have not been used to study splicing changes in heart disease.

Functional effects of glucose transporters in human ventricular myocardium.

Aims: Insulin-dependent positive inotropic effects (PIE) are partially Ca(2+) independent. This mechanism is potentially glucose dependent. In contrast to most animal species, human myocardium expresses high levels of sodium-glucose-transporter-1 (SGLT-1) mRNA besides the common glucose-transporters-1 and -4 (GLUT1, GLUT4).

Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy.

Background: RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. Here, we report on targeted RNAi for the treatment of heart failure, an important disorder in humans that results from multiple causes. Successful treatment of heart failure is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban, a key regulator of cardiac Ca(2+) homeostasis.

Mechanistic insight into the functional and toxic effects of Strophanthidin in the failing human myocardium.

Background: Cardiac glycosides are characterized by a narrow therapeutic range with Ca2+-overload and arrhythmias occurring at higher concentrations. Data on cardiac glycosides in isolated failing human myocardium are scarce and the frequency-dependent actions and toxicity of Strophanthidin have not yet been characterized.

Aims: To determine inotropic responses and toxicity of Strophanthidin in failing human myocardium.