Clinical Research

Cardiac tissue engineering could be useful for replacement and/or repair of diseased or malformed cardiac tissue. The creation of functional, biocompatible contractile tissues, however, remains challenging. These investigators report a novel method of engineering a highly effective collagen-cell scaffold based on arginine–glycine–aspartic acid–serine peptides cross-linked to a clinically approved collagen matrix.

Apoptosis contributes notably to the pathogenesis of heart failure, but these investigators found that upregulation of endogenous antiapoptotic mechanisms counterbalance the death-receptor and mitochondrial apoptotic pathways. Concurrent activation of antiapoptotic factors can interrupt the apoptotic cascade, prevent cell loss despite the presence of multiple proapoptotic factors, and could offer an opportunity for therapeutic intervention.

Elevated lipoprotein (a) concentrations are associated with atherothrombotic complications of coronary artery disease. In this study, combined lipid apheresis and lipid-lowering medication was efficacious in reducing extremely high levels of lipoprotein (a), and thus in preventing major adverse coronary events, in patients in whom maximally tolerated doses of medication alone had failed to control events associated with coronary artery disease.

Ventricular assist devices (VADs) are associated with thromboembolic events. Aspirin hyporesponsiveness has been associated with an increased risk of future vascular atherothrombotic events, such as acute coronary syndromes and cerebrovascular accidents, but whether this disorder can predict future clinical thromboembolic events in patients with VADs remains unclear. In this article, the prevalence and clinical relevance of aspirin hyporesponsiveness before and after VAD implantation and the role of markers of coagulation and fibrinolysis were assessed.

Early detection of atherosclerosis is beneficial but the reliability of imaging techniques is unclear. This study assesses reproducibility for black-blood MRI measurement of atherosclerotic burden in the left and right carotid arteries and the thoracic descending aorta. The results suggest that measurement of some MRI parameters is reliable, and the researchers recommend further investigation of their value for predicting cardiovascular disease.

Augoustides et al. present a risk stratification system based on ischemic pattern at presentation in patients with acute type A aortic dissection. The authors believe that, with further validation, the Penn classification system could be used to identify high-risk groups of patients for further intervention and to facilitate future trial design.

Coronary allograft vasculopathy is a severe complication of heart transplantation. In this paper, the authors used virtual histology intravascular ultrasound to characterize plaque burden and tissue composition over time in vessels of heart transplant recipients. Knowledge of the relationship between changes in plaque composition and clinical outcome might facilitate identification of high-risk patients who require more aggressive medical therapy.

Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction. In this paper patients with left ventricular ejection fraction less than 45% after acute myocardial infarction were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3–6 weeks or 3–4 months after AMI. Their data shows that combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.

Mitochondria of circulating white blood cells (WBC) and platelets sense oxidative stress during capillary passage and react by producing reactive oxygen species (ROS). Evidence indicates that congestive heart failure (CHF) is associated with oxidative stress; however, the role of WBC and platelets as mediators in CHF has not been investigated. In this paper the authors conducted an observational study to investigate the degree of oxidation in WBC and platelets in patients with CHF and healthy volunteers. Their data shows that in CHF, the proportion of WBC and platelets that are ROS positive is raised. The raised numbers of circulating ROS-positive WBC and platelets amplify oxidative stress in CHF.

Aortic dilatation is common among adults with bicuspid aortic valves (BAV). Predictors of risk and progression of aortic dilatation are not well described in this setting. In this retrospective analysis the authors study data on the presence of dilation in several aortic segments in 156 adult patients with BAV who had serial echocardiograms performed at least 1 year apart. Their data shows that patients with BAV and increased age, high body surface area, and moderate to severe aortic regurgitation are more likely to have a dilated aorta. Patients with right-to-left leaflet fusion are at increased risk of rapid aortic dilatation.

Because octogenarian patients have not been adequately represented in randomized trials comparing CABG and PCI, the most appropriate method of revascularization for this group of patients has not been determined. In this paper the authors performed a systematic review and a meta-analysis of 66 studies of coronary revascularization in patients aged over 80 years. Their data shows that revascularization can be performed in octogenarians with acceptable short-term and long-term outcomes. Furthermore, it is unclear whether octogenarians derive greater survival benefit from CABG or from PCI because preprocedural risk profiles differ between intervention types.

Several known candidate gene variants are useful markers for diagnosing hyperlipoproteinemia. In this paper the authors evaluate the association of two commonAPOA5 single-nucleotide polymorphisms across the range of classic hyperlipoproteinemia phenotypes. Their data shows that a high proportion of patients with four classic hyperlipoproteinemia phenotypes are carriers of either the APOA5S19W or −1131T>C variant or both. The authors conclude that these two variants are robust genetic biomarkers of a range of clinical hyperlipoproteinemia phenotypes linked by hypertriglyceridemia.

Studies of the transplantation of autologous bone marrow cells (BMCs) in patients with chronic ischemic heart disease have assessed effects on viable, peri-infarct tissue. In this paper the authors conducted a single-blinded, randomized, controlled study to investigate whether intramuscular or intracoronary administration of BMCs into nonviable scarred myocardium during CABG improves contractile function of scar segments compared with CABG alone. Their data shows that injection of autologous BMCs directly into the scar or into the artery supplying the scar is safe but does not improve contractility of nonviable scarred myocardium, reduce scar size, or improve left ventricular function more than CABG alone.

The time course of events after acute coronary syndromes (ACS) might influence the timing and duration of therapeutic interventions. In this paper the authors study the timing of death, reinfarction, stroke, and major bleeding within 6 months of ACS in 46,829 patients enrolled in the Global Registry of Acute Coronary Events (GRACE). Their data shows that the timing of events after ACS was affected by ST category and influenced by GRACE risk score within each electrocardiographic category of ACS. They recommend that risk stratification should, therefore, include multiple risk factors rather than ST shift alone.

Endothelial dysfunction is an early manifestation of atherosclerotic disease. Circulating cells that express CD34, including endothelial and hematopoietic progenitor cells, might play a part in the development and progression of atherosclerosis. In this paper the authors evaluate the association between coronary endothelial dysfunction and concentrations of circulating CD34⁺cell subsets.

Cardiac rehabilitation, in most developed countries, is a proven means of reducing mortality but it is grossly underutilized owing to factors involving both the health system and patients. These issues have not been investigated concurrently. In this paper the authors describe a prospective study with a multilevel design to show that the most relevant physician perceptions of such programs are program quality and perceived benefit. For patients, they are barriers to cardiac rehabilitation, which might be conveyed during pre-referral discussions. Work to improve physicians' perceptions and patients' understanding of rehabilitation services might improve use.

Many coronary heart disease patients fail to reach recommended LDL levels, either due to intolerance or inadequate response to available lipid-lowering therapy. Microsomal triglyceride transfer protein (MTP) inhibitors may provide a novel alternative pathway for LDL lowering. In this paper the authors tested the safety and LDL lowering efficacy of the MTP inhibitor, AEGR-733, alone and in combination with ezetimibe.

Leptin may be a key regulator of C-reactive protein (CRP) levels, which in turn, is a marker of systemic inflammation. Both leptin and CRP are predictors of cardiovascular disease (CVD). High leptin levels are independently associated with CVD even after adjustment for CRP; elevated CRP levels are not associated with CVD after adjustment for leptin. However, subjects with increased leptin and CRP are at the highest risk for CVD.

The custom microenvironment “vascular niche” is a potential therapeutic target for several pathophysiological conditions. Osteoblasts act as regulators of the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor may increase the number of cells mobilized into the bloodstream. The authors demonstrate that PTH may enhance the efficiency of hematopoietic stem cell-based therapy in a recognized model of peripheral ischemia.

Rheumatic heart disease is an important problem in developing countries but many cases are detected only when the disease has progressed to cardiac failure. Screening can detect cases earlier, but there are no screening guidelines. In this paper the authors describe a novel screening protocol and report a high echocardiographically confirmed prevalence of rheumatic heart disease among Tongan schoolchildren.