Coronary revascularization and TAVI: before, during, after or never?

Aortic valve stenosis and coronary artery disease (CAD) frequently coexist in elderly patients selected for transcatheter aortic valve implantation (TAVI). Therapeutic strategies to manage concomitant obstructive CAD are therefore an important consideration in the overall management of patients with severe aortic stenosis (AS) undergoing TAVI. Conventional surgical aortic valve replacement and coronary artery bypass grafting is the treatment of choice for low and intermediate risk patients with symptomatic severe AS and concomitant obstructive CAD. However, TAVI and percutaneous coronary intervention (PCI) are viable alternative options for high-risk or inoperable patients presenting with symptomatic severe AS. PCI has been shown to be feasible and safe in selected high-risk or inoperable patients with symptomatic severe AS. However, the optimal timing of PCI relative to the TAVI procedure has been a subject of debate. The most frequent approch is staged PCI typically performed a few weeks prior to TAVI. However, concomitant PCI has also been shown to be a feasible and safe approach, particularly in patients with a low level of CAD complexity and an absence of severe renal impairment. Conversely, staged PCI should be considered in patients with higher degrees of CAD complexity, particularly in the presence of severe renal impairment. The aim of the present review is to discuss the safety and feasibility of performing PCI in elderly patients with severe AS and the optimal timing of PCI relative to the TAVI procedure using the most up-to-date available evidence.

Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor.

BACKGROUND: Vascular smooth muscle cell hyperplasia with resulting luminal narrowing is the main histologic feature of accelerated arteriosclerosis seen after organ transplantation (transplant arteriosclerosis) and after balloon angioplasty (restenosis). It limits long-term allograft survival, as well as the success rate of angioplasty. At present, effective prophylactic and therapeutic strategies for these complications are still missing. Studies of in vivo models of accelerated arteriosclerosis induced by allogeneic or mechanical injury to the vasculature indicate that certain immunosuppressive drugs have inhibitory properties on smooth muscle cell hyperplasia. METHODS: This study summarizes the inhibitory effects of different immunosuppressive drugs in vitro on the growth factor-induced proliferation of vascular smooth muscle cells and endothelial cells isolated from human and rat thoracic aortas. RESULTS: The immunosuppressants rapamycin and mycophenolic acid were potent in inhibiting smooth muscle and endothelial cell proliferation. Cyclosporine demonstrated some inhibition of smooth muscle and endothelial cell proliferation, but the inhibitory concentration50 (IC50) values were just below toxicity levels. FK506 revealed a moderate inhibitory activity but, interestingly, only for human cells. High concentrations of leflunomide inhibited in our experiments only rat smooth muscle and endothelial cell proliferation. Methylprednisolone showed a gradual inhibition over a broad concentration interval of rat and human smooth muscle cells and of rat but not of human endothelial cells. CONCLUSIONS: These data indicate that all of the established and new immunosuppressants tested have antiproliferative properties on vascular cells. Rapamycin was by far the most potent one. Therefore immunosuppressants, especiallyrapamycin and mycophenolic acid, may be used for prevention of accelerated arteriosclerosis.