Évaluation de la perfusion myocardique par TEP-TDM. [Myocardial perfusion imaging using PET/CT.]

For the past decade, PET and PET/CT have been widely studied for myocardial perfusion imaging. Several studies demonstrated the incremental value of PET for the diagnostic and prognostic assessment of patients with coronary artery disease. Moreover, PET allows for non-invasively quantifying myocardial blood flow and myocardial flow reserve, that both are recognized as surrogate marker of cardiac event free survival. By enabling the exploration of epicardial disease and the microvasculature, PET constitutes a unique tool to study pathophysiogical mechanisms leading to atherosclerosis genesis. The recent emergence of high-tech hybrid machines may even provide further incremental information about coronary function and morphology. By taking the best of each modality, a better assessment of patients with coronary artery disease is expected. (C) 2011 Elsevier Masson SAS. All rights reserved.

Role of Mitogen-Activated Protein Kinases in Myocardial Ischemia-Reperfusion Injury during Heart Transplantation.

In solid organ transplantation, ischemia/reperfusion (IR) injury during organ procurement, storage and reperfusion is an unavoidable detrimental event for the graft, as it amplifies graft inflammation and rejection. Intracellular mitogen-activated protein kinase (MAPK) signaling pathways regulate inflammation and cell survival during IR injury. The four best-characterized MAPK subfamilies are the c-Jun NH2-terminal kinase (JNK), extracellular signal- regulated kinase-1/2 (ERK1/2), p38 MAPK, and big MAPK-1 (BMK1/ERK5). Here, we review the role of MAPK activation during myocardial IR injury as it occurs during heart transplantation. Most of our current knowledge regarding MAPK activation and cardioprotection comes from studies of preconditioning and postconditioning in nontransplanted hearts. JNK and p38 MAPK activation contributes to myocardial IR injury after prolonged hypothermic storage. p38 MAPK inhibition improves cardiac function after cold storage, rewarming and reperfusion. Small-molecule p38 MAPK inhibitors have been tested clinically in patients with chronic inflammatory diseases, but not in transplanted patients, so far. Organ transplantation offers the opportunity of starting a preconditioning treatment before organ procurement or during cold storage, thus modulating early events in IR injury. Future studies will need to evaluate combined strategies including p38 MAPK and/or JNK inhibition, ERK1/2 activation, pre- or postconditioning protocols, new storage solutions, and gentle reperfusion.

Multi-slice three-dimensional myocardial strain tensor quantification using zHARP.

In this article we propose a novel method for calculating cardiac 3-D strain. The method requires the acquisition of myocardial short-axis (SA) slices only and produces the 3-D strain tensor at every point within every pair of slices. Three-dimensional displacement is calculated from SA slices using zHARP which is then used for calculating the local displacement gradient and thus the local strain tensor. There are three main advantages of this method. First, the 3-D strain tensor is calculated for every pixel without interpolation; this is unprecedented in cardiac MR imaging. Second, this method is fast, in part because there is no need to acquire long-axis (LA) slices. Third, the method is accurate because the 3-D displacement components are acquired simultaneously and therefore reduces motion artifacts without the need for registration. This article presents the theory of computing 3-D strain from two slices using zHARP, the imaging protocol, and both phantom and in-vivo validation.

Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.

AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

A hypoxic episode during cardiogenesis downregulates the adenosinergic system and alters the myocardial anoxic tolerance.

To what extent hypoxia alters the adenosine (ADO) system and impacts on cardiac function during embryogenesis is not known. Ectonucleoside triphosphate diphosphohydrolase (CD39), ecto-5'-nucleotidase (CD73), adenosine kinase (AdK), adenosine deaminase (ADA), equilibrative (ENT1,3,4), and concentrative (CNT3) transporters and ADO receptors A1, A2A, A2B, and A3 constitute the adenosinergic system. During the first 4 days of development chick embryos were exposed in ovo to normoxia followed or not followed by 6 h hypoxia. ADO and glycogen content and mRNA expression of the genes were determined in the atria, ventricle, and outflow tract of the normoxic (N) and hypoxic (H) hearts. Electrocardiogram and ventricular shortening of the N and H hearts were recorded ex vivo throughout anoxia/reoxygenation ± ADO. Under basal conditions, CD39, CD73, ADK, ADA, ENT1,3,4, CNT3, and ADO receptors were differentially expressed in the atria, ventricle, and outflow tract. In H hearts ADO level doubled, glycogen decreased, and mRNA expression of all the investigated genes was downregulated by hypoxia, except for A2A and A3 receptors. The most rapid and marked downregulation was found for ADA in atria. H hearts were arrhythmic and more vulnerable to anoxia-reoxygenation than N hearts. Despite downregulation of the genes, exposure of isolated hearts to ADO 1) preserved glycogen through activation of A1 receptor and Akt-GSK3β-GS pathway, 2) prolonged activity and improved conduction under anoxia, and 3) restored QT interval in H hearts. Thus hypoxia-induced downregulation of the adenosinergic system can be regarded as a coping response, limiting the detrimental accumulation of ADO without interfering with ADO signaling.

Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse.

Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response important for myocardial healing, but which may also contribute to adverse ventricular remodelling. Such inflammation is initiated by molecular danger signals released by damaged myocardium, which induce innate immune responses by activating toll-like receptors (TLRs). Detrimental roles have been recently reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore evaluated the role of TLR5, expressed at high level in the heart, in the development of myocardial damage and inflammation acutely triggered by MIR. TLR5-/- and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h reperfusion). We measured infarct size, markers of cardiac oxidative stress, myocardial phosphorylation state of mitogen-activated protein (MAP) kinases and AKT, expression levels of chemokines and cytokines in the heart and plasma, as well as cardiac function by echography and conductance volumetry. TLR5-deficient mice had normal cardiac morphology and function under physiological conditions. After MIR, the absence of TLR5 promoted an increase in infarct size and myocardial oxidative stress. Lack of TLR5 fostered p38 phosphorylation, reduced AKT phosphorylation and markedly increased the expression of inflammatory cytokines, whereas it precipitated acute LV (left ventricle) dysfunction. Therefore, contrary to the detrimental roles of TLR2, TLR3 and TLR4 in the infarcted heart, TLR5 is important to limit myocardial damage, inflammation and functional compromise after MIR.

Incidence and consequence of major bleeding in primary percutaneous intervention for ST-elevation myocardial infarction in the era of radial access: an analysis of the international randomized Acute myocardial infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up trial.

AIMS: The aims of the study are to compare the outcome with and without major bleeding and to identify the independent correlates of major bleeding complications and mortality in patients described in the ATOLL study. METHODS: The ATOLL study included 910 patients randomly assigned to either 0.5 mg/kg intravenous enoxaparin or unfractionated heparin before primary percutaneous coronary intervention. Incidence of major bleeding and ischemic end points was assessed at 1 month, and mortality, at 1 and 6 months. Patients with and without major bleeding complication were compared. A multivariate model of bleeding complications at 1 month and mortality at 6 months was realized. Intention-to-treat and per-protocol analyses were performed. RESULTS: The most frequent bleeding site appears to be the gastrointestinal tract. Age >75 years, cardiac arrest, and the use of insulin or >1 heparin emerged as independent correlates of major bleeding at 1 month. Patients presenting with major bleeding had significantly higher rates of adverse ischemic complications. Mortality at 6 months was higher in bleeders. Major bleeding was found to be one of the independent correlates of 6-month mortality. The addition or mixing of several anticoagulant drugs was an independent factor of major bleeding despite the predominant use of radial access. CONCLUSIONS: This study shows that major bleeding is independently associated with poor outcome, increasing ischemic events, and mortality in primary percutaneous coronary intervention performed mostly with radial access.