In statin-treated patients with low HDL-C, high-dose modified-release NA, compared with placebo, significantly reduces carotid atherosclerosis within 12 months. (Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function; NCT00232531).
The limited efficacy of current treatment strategies for targeting atherosclerosis and its complications requires new therapeutic options to be explored. From early fatty-streak lesions to advanced plaques, macrophage-derived foam cells are integral to the development and progression of atherosclerosis. Elucidation of molecular and cellular processes involving macrophages has led to numerous therapeutic targets being suggested. Potential sites of intervention range from monocyte recruitment, through cholesterol uptake and esterification, to cholesterol evacuation and macrophage egress from plaque. In addition, complex patterns of transcriptional regulation of genes involved in macrophage lipid homeostasis and in the regulation of inflammation have been partly unraveled. Recognition of ATP-binding cassette cholesterol transport mechanisms and cellular interactions with cholesterol-accepting apolipoproteins (or synthetic mimetics) opens up new potential therapies to induce atherosclerosis regression in humans. This review presents a systematic evaluation of actual and potential macrophage-directed pharmacologic interventions. It reflects the timely convergence of three important strands: advances in molecular and cell biology that have suggested therapeutic targets in macrophages; the development of multiple classes of drugs targeting these pathways; and the emergence of sensitive imaging techniques that have enabled identification of changes in plaque size and composition in response to treatment.
Consecutive patients with paroxysmal AF undergoing PVI under general anesthesia with 1 of 2 experienced operators were recruited. Each operator had procedural experience of >500 PVIs with a minimum of 50 procedures/year. All patients provided written informed consent to the study protocol, which had been approved by the Melbourne Health Human Research Ethics Committee.
PVI ProcedureIntracardiac catheters were positioned as follows: (1)
EGM characteristics do not reliably predict either CF before the onset of RF, nor do they predict the likelihood of an effective lesion. CF parameters were superior to power, temperature, and impedance changes during RF in predicting lesion efficacy.
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