The presence of angiographic collaterals in non-ST elevation myocardial infarction is a predictor of long-term clinical outcomes.

OBJECTIVES: To determine whether the presence of angiographic coronary collaterals is a predictor of long-term clinical outcomes in patients with non-ST elevation myocardial infarction (NSTEMI). BACKGROUND: The presence of coronary collaterals on angiography provides prognostic information in patients with STEMI, but it is unknown whether they provide prognostic information in patients with NSTEMI. METHODS: This was a prospective cohort study of 931 consecutive patients undergoing coronary angiography of which 269 (29%) had a NSTEMI. Baseline characteristics, angiographic details, and long-term clinical outcomes including death, recurrent MI, coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), stroke, and congestive heart failure (CHF) were collected. Each clinical outcome as well as the combined endpoint of death, recurrent MI, CABG, PCI stroke and CHF was compared in subjects with and without collaterals. RESULTS: At one year, individuals with collaterals had significantly increased rates of the combined endpoint compared with those without (25% vs. 16%, P = 0.0001). On multivariate analysis, the presence of collaterals was a strong predictor of the combined endpoint of death, recurrent MI, CABG, PCI, stroke and CHF (HR 1.95, CI 95% 1.08-3.52; P = 0.027). Similarly, in the subset of 115 patients (43%) in whom the culprit artery was identified, the presence of collaterals was a strong negative predictor (HR 3.71, CI 1.31-10.57, P = 0.014), driven by a 13-fold increase in subsequent CABG. CONCLUSIONS: In patients with NSTEMI the presence of angiographic coronary collaterals is a predictor of long-term clinical outcomes primarily driven by increased rates of surgical revascularization.

A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen.

To enable arrayed or pooled loss-of-function screens in a wide range of mammalian cell types, including primary and nondividing cells, we are developing lentiviral short hairpin RNA (shRNA) libraries targeting the human and murine genomes. The libraries currently contain 104,000 vectors, targeting each of 22,000 human and mouse genes with multiple sequence-verified constructs. To test the utility of the library for arrayed screens, we developed a screen based on high-content imaging to identify genes required for mitotic progression in human cancer cells and applied it to an arrayed set of 5,000 unique shRNA-expressing lentiviruses that target 1,028 human genes. The screen identified several known and approximately 100 candidate regulators of mitotic progression and proliferation; the availability of multiple shRNAs targeting the same gene facilitated functional validation of putative hits. This work provides a widely applicable resource for loss-of-function screens, as well as a roadmap for its application to biological discovery.