Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.

CMR is a valuable adjunct to conventional investigations in a diagnostically challenging and important group of patients with troponin-positive chest pain and unobstructed coronary arteries.

Free-breathing 3D coronary MR angiography can be used to identify the proximal anatomy of anomalous coronary arteries.

Rationale:Patients with acute coronary syndrome (ACS) predisposed to recurrent coronary events have an expansion of a distinctive T-cell subset, the CD4 ؉ CD28 null T cells. These cells are highly inflammatory and cytotoxic in spite of lacking the costimulatory receptor CD28, which is crucial for optimal T cell function. The mechanisms that govern CD4 ؉ CD28null T cell function are unknown.Objective: Our aim was to investigate the expression and role of alternative costimulatory receptors in CD4 ؉ CD28 null T cells in ACS. Methods and Results: Expression of alternative costimulatory receptors (inducible costimulator, OX40, 4 -1BB,cytotoxic T lymphocyte associated antigen-4, programmed death-1) was quantified in CD4 ؉ CD28 null T cells from circulation of ACS and stable angina patients. Strikingly, in ACS, levels of OX40 and 4-1BB were significantly higher in circulating CD4 ؉ CD28null T cells compared to classical CD4 ؉ CD28 ؉ T lymphocytes. This was not observed in stable angina patients. Furthermore, CD4؉ CD28 null T cells constituted an important proportion of CD4 ؉ T lymphocytes in human atherosclerotic plaques and exhibited high levels of OX40 and 4-1BB. In addition, the ligands for OX40 and 4-1BB were present in plaques and also expressed on monocytes in circulation. Importantly, blockade of OX40 and 4-1BB reduced the ability of CD4 ؉ CD28null T cells to produce interferon-␥ and tumor necrosis factor-␣ and release perforin. Key Words: atherosclerosis Ⅲ coronary disease Ⅲ immune system Ⅲ lymphocytes Ⅲ receptors C oronary artery disease continues to be the leading cause of death in the developed world. Recent research has demonstrated that coronary artery disease results from an uncontrolled immune response and T lymphocytes have a central role in the development and progression of the disease. 1,2 Detailed analysis of CD4 ϩ T cells in coronary artery disease unveiled an increased frequency of a distinctive subset of lymphocytes called CD4 ϩ CD28 Conclusions: Costimulatory pathways are altered in CD4؉null T cells. 3 These cells are characterized by the lack of CD28, the main costimulatory receptor that regulates the response of T lymphocytes to antigen. 4 The CD4 ϩ CD28null T cell subset is present in low frequencies in healthy individuals and has also been shown to increase in patients with chronic inflammatory diseases such as autoimmunity. 5 In coronary artery disease, the frequency of CD4 The proinflammatory features of CD4 ϩ CD28 null T lymphocytes are surprising, as the activation and survival of T cells depends on costimulatory signals delivered via the CD28 receptor. 4 The activation of T cells requires not only the recognition of antigen, but also a second signal delivered by the interaction of the CD28 costimulatory receptor on T cells with its ligands on antigen presenting cells. 4 CD28 signaling controls the expression of interleukin-2 receptors and the production of interleukin-2 by activated T cells, which enable their proliferation, differentiation into effectors and survival. 12 Indeed, in th...

AimDespite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this doubleblind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI).Methods and resultsA total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6–8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6–8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size −0.7% 95% CI: −2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6–8 days and at 6 months and final infarct size (FIS) measured at 6 months.ConclusionsSodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size.