Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

Adaptive changes to oxygen availability are critical for cell survival and tissue homeostasis. Prolonged oxygen deprivation due to reduced blood flow to cardiac or peripheral tissues can lead to myocardial infarction and peripheral vascular disease, respectively. Mammalian cells respond to hypoxia by modulating oxygen-sensing transducers that stabilize the transcription factor hypoxia-inducible factor 1α (HIF-1α), which transactivates genes governing angiogenesis and metabolic pathways. Oxygen-dependent changes in HIF-1α levels are regulated by proline hydroxylation and proteasomal degradation. Here we provide evidence for what we believe is a novel mechanism regulating HIF-1α levels in isolated human ECs during hypoxia. Hypoxia differentially increased microRNA-424 (miR-424) levels in ECs. miR-424 targeted cullin 2 (CUL2), a scaffolding protein critical to the assembly of the ubiquitin ligase system, thereby stabilizing HIF-α isoforms. Hypoxia-induced miR-424 was regulated by PU.1-dependent transactivation. PU.1 levels were increased in hypoxic endothelium by RUNX-1 and C/EBPα. Furthermore, miR-424 promoted angiogenesis in vitro and in mice, which was blocked by a specific morpholino. The rodent homolog of human miR-424, mu-miR-322, was significantly upregulated in parallel with HIF-1α in experimental models of ischemia. These results suggest that miR-322/424 plays an important physiological role in post-ischemic vascular remodeling and angiogenesis.

Cardiovascular magnetic resonance provides insights into myocardial structure and function noninvasively, with high diagnostic accuracy and without ionizing radiation. Myocardial tissue characterization in particular gives cardiovascular magnetic resonance a prime role among all the noninvasive cardiovascular investigations. Late gadolinium enhancement imaging is an established method for visualizing replacement scar, providing diagnostic and prognostic information in a variety of cardiac conditions. Late gadolinium enhancement, however, relies on the regional segregation of tissue characteristics to generate the imaging contrast. Thus, myocardial pathology that is diffuse in nature and affecting the myocardium in a rather uniform and global distribution is not well visualized with late gadolinium enhancement. Examples include diffuse myocardial inflammation, fibrosis, hypertrophy, and infiltration. T1 mapping is a novel technique allowing to diagnose these diffuse conditions by measurement of T1 values, which directly correspond to variation in intrinsic myocardial tissue properties. In addition to providing clinically meaningful indices, T1-mapping measurements also allow for an estimation of extracellular space by calculation of extracellular volume fraction. Multiple lines of evidence suggest a central role for T1 mapping in detection of diffuse myocardial disease in early disease stages and complements late gadolinium enhancement in visualization of the regional changes in common advanced myocardial disease. As a quantifiable measure, it may allow grading of disease activity, monitoring progress, and guiding treatment, potentially as a fast contrast-free clinical application. We present an overview of clinically relevant technical aspects of acquisition and processing, and the current state of art and evidence, supporting its clinical use.