The emergence of the global pandemic of chronic diseases necessitates critical assessment of interventions that can be targeted at both the individual and population levels. Among cardiovascular diseases, the increasing prevalence of valvular heart diseases such as aortic stenosis parallels the rising burden of atherosclerotic cardiovascular diseases. As an alternative to surgical aortic valve replacement, technological innovation has allowed development of minimally invasive transcatheter aortic valve replacement (TAVR). This review examines whether TAVR can be applicable in low-resource regions across the world. Although revolutionary, TAVR is currently complex and requires a "Heart Team" approach for optimized patient care. We propose the emergence of telemedicine networks, newer valve designs that allow implementation of minimal approaches, and the use of minimal numbers of specialists for adapting TAVR to settings where surgical backup is not available. With efforts to reduce resource utilization, these alternate strategies have the potential to affect implementation of TAVR globally.

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Background. Current lipid-lowering drugs often leave significant residual risk for adverse outcomes. Identification of previously approved drugs for new indications, drug repurposing, may provide a cost effective alternative to de novo drug developing.Objectives. We combined clinical, transcriptomic, computational, and experimental strategies to explore lipid-lowering and plaque-stabilizing effects of atypical antidepressant trazodone.Methods. First, a connectivity mapping strategy was used to match rosuvastatin gene expression signature derived from a clinical trial of 85 patients with to the expression patterns of 1,309 different small molecules to discover a similarity between the rosuvastatin and trazodone gene expression signatures. Then, we assessed the lipid-lowering ability of trazodone in vitro using HepG2 cells and in vivo using molecular imaging of rabbit atherosclerotic lesions. In addition, we analyzed electronic medical records of patients from three large medical centers who had a prescription for trazodone and lipid laboratory measurements available.Results. Trazodone significantly reduced cholesterol levels in the HepG2 human hepatocyte model, decreased atherosclerotic plaque burden in a rabbit model and lowered low-density lipoprotein (LDL) cholesterol levels in patients.Conclusion. Our results indicate that trazodone may be a promising candidate for adjunctive lipid lowering therapy. It may provide significant benefits to patients with hyperlipidemia, including lipid level reduction and formation of a more favorable atherosclerotic plaque morphology. Patients diagnosed with major depressive disorder requiring better lipid control would benefit the most from the for adjunctive lipid lowering therapy.

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