Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease.

Background: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.

Objectives: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness.

Background: The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction.

Methods And Results: By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.

Cardiac Resynchronization Therapy in CKD Stage 4 Patients.

Background And Objectives: Cardiac resynchronization therapy (CRT) is a well established heart failure treatment that has shown to improve renal function. However, landmark CRT trials excluded patients with severe renal dysfunction. Therefore, this study evaluated the effect of CRT on renal function and long-term prognosis in patients with stage 4 CKD.

LDL cholesterol still a problem in old age? A Mendelian randomization study.

Background: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underestimated. In the current study, we used an LDL genetic risk score (GRS) to overcome this problem.

Electrocardiographic T wave and its relation with ventricular repolarization along major anatomical axes.

Background: The genesis of the electrocardiographic T wave is incompletely understood and subject to controversy. We have correlated the ventricular repolarization sequence with simultaneously recorded T waves.

Methods And Results: Nine pig hearts were Langendorff-perfused (atrial pacing, cycle length 650 ms).

Left ventricular reverse remodeling, device-related adverse events, and long-term outcome after cardiac resynchronization therapy in the elderly.

Background: Limited data are available on efficacy, safety, and long-term prognosis after cardiac resynchronization therapy (CRT) in elderly patients. We aimed at evaluating the effect of CRT, device-related adverse events, and long-term outcome after CRT among elderly patients.

Methods And Results: A total of 798 CRT recipients (208 elderly: age, ≥75 years; 590 nonelderly: age, <75 years) underwent clinical and echocardiographic evaluation at baseline and 6-month follow-up.

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.

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial.

Importance: Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.

Objective: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes.

Toll-like receptor 4 inhibitor TAK-242 treatment does not influence perfusion recovery in tissue ischemia.

Toll-like receptors (TLRs) are important in innate immune responses, which are crucial in collateral artery formation (arteriogenesis). TLR4⁻/⁻ mice undergoing hind limb ischemia show decreased perfusion recovery accompanied by an impaired infiltration of inflammatory cells. TLR antagonists are currently developed and tested with the objective to inhibit acute exacerbation of organ damaging immune responses.

Left-dominant arrhythmogenic cardiomyopathy in a large family: associated desmosomal or nondesmosomal genotype?

Background: Arrhythmogenic cardiomyopathy (AC) is considered a predominantly right ventricular (RV) desmosomal disease. However, left-dominant forms due to desmosomal gene mutations, including PKP2 variant c.419C>T, have been described.

Postconditioning against ischaemia-reperfusion injury: ready for wide application in patients?

Ischaemic postconditioning (IPOC) is an intervention in which brief, intermittent periods of reocclusion at the onset of reperfusion (i.e. stuttering reperfusion) protect myocardium from lethal reperfusion injury.

Echocardiographic tissue deformation imaging quantifies abnormal regional right ventricular function in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Background: The aim of this study was to determine the accuracy of new quantitative echocardiographic strain and strain-rate imaging parameters to identify abnormal regional right ventricular (RV) deformation associated with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).

Methods: A total of 34 patients with ARVD/C (confirmed by Task Force criteria) and 34 healthy controls were prospectively enrolled. Conventional echocardiography, including Doppler tissue imaging (DTI), was performed.

Ultrasound and microbubble-targeted delivery of therapeutic compounds: ICIN Report Project 49: Drug and gene delivery through ultrasound and microbubbles.

The molecular understanding of diseases has been accelerated in recent years, producing many new potential therapeutic targets. A noninvasive delivery system that can target specific anatomical sites would be a great boost for many therapies, particularly those based on manipulation of gene expression. The use of microbubbles controlled by ultrasound as a method for delivery of drugs or genes to specific tissues is promising.

Clinical application of three-dimensional echocardiography: past, present and future.

Significant advances in three-dimensional echocardiography have made this modality a powerful diagnostic tool in the cardiology clinic. It can provide accurate and reliable measurements of chamber size and function, including the quantification of left ventricular mechanical dyssynchrony to guide patient selection for cardiac resynchron-isation therapy. Furthermore, three-dimensional echocardiography offers novel views and comprehensive anatomic definition of valvular and congenital abnormalities, improving diagnosis and preoperative planning.

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

During the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention.

Differences in distribution of fibrosis in the ventricles underlie dominant arrhythmia vulnerability of the right ventricle in senescent mice.

Mutations that are supposed to affect right (RV) and left ventricular (LV) electrophysiology equally, often reveal dominant conduction slowing and arrhythmia vulnerability in RV. In this study we investigated the mechanism of dominant arrhythmia vulnerability of RV in senescent mice. We performed epicardial ventricular activation mapping on adult and senescent Langendorff perfused hearts.

High shear stress influences plaque vulnerability Part of the data presented in this paper were published in Stroke 2007;38:2379-81.

Shear stress of the blood at the vessel wall plays an important role in many processes in the cardiovascular system primarily focused on the regulation of vessel lumen and wall dimensions. There is ample evidence that atherosclerotic plaques are generated at low shear stress regions in the cardiovascular system, while high shear stress regions are protected. In the course of plaque progression, advanced plaques start to encroach into the lumen, and thereby start to experience high shear stress at the endothelium.

'No-reflow' after acute myocardial infarction: direct visualisation of microvascular obstruction by gadolinium-enhanced CMR.

Cardiovascular magnetic resonance is considered the standard imaging modality in clinical trials to monitor patients after acute myocardial infarction. However, limited data are available with respect to infarct size, presence and extent of microvascular injury (MVO) and changes over time, in relation to cardiac function in optimally treated patients. In the current study we prospectively investigate the change of infarct size over time, and the incidence and significance of MVO in a uniform, optimally treated patient group after AMI.

Cardiomyocytes from human embryonic stem cells: more than heart repair alone.

One of the most-exciting and controversial discoveries of the last decade has been the isolation of embryonic stem cells from human embryos. The capacity of these cells to form all somatic cell types in the human body has captured the imagination of researcher and clinician alike, the perspectives that they represent for cell replacement therapies in multiple chronic disorders being used to justify the use of embryos for this purpose. However, there is a gradual realization that cell therapies are in the far future and some find that the other, more immediately applicable, types of research give less justification for the use of embryos.

Cardiomyocytes from human embryonic stem cells.

Terminal heart failure is characterized by a significant loss of cardiac myocytes. Stem cells represent a possibility for replacing these lost myocytes but the question of which stem cells are most ideally suited for cell transplantation therapies is still being addressed. Here, we consider human embryonic stem cells (HESC), derived from human embryos in this context.