Background-The purpose of this study was to determine the efficacy of stent-based delivery of sirolimus (SRL) alone or in combination with dexamethasone (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle progression. Methods and Results-Stents were coated with a nonerodable polymer containing 185 g SRL, 350 g DEX, or 185 g SRL and 350 g DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, nϭ13; SRL, nϭ13; DEX, nϭ13; SRL and DEX, nϭ8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97Ϯ13 ng/artery, with a stent content of 71Ϯ10 g at 3 days. At 7 days, proliferating cell nuclear antigen and retinoblastoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47Ϯ1.04 mm 2 for the SRL alone and 2.42Ϯ1.04 mm 2 for the combination of SRL and DEX compared with the metal (5.06Ϯ1.88 mm 2 , PϽ0.0001) or DEX-coated stents (4.31Ϯ3.21 mm 2 , PϽ0.001), resulting in a 50% reduction of percent in-stent stenosis. Conclusions-Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.

In Part I of this article, the definitions, prevalence, and clinical presentation of chronic total occlusions (CTOs) were reviewed, the histopathology of CTOs was examined, efforts to replicate human CTOs with experimental models were appraised, and the clinical relevance and rationale for CTO revascularization were evaluated. 1 In Part II, we summarize the technical approach to and outcomes after percutaneous coronary intervention (PCI) of occluded coronary arteries, describe the novel devices and drugs approved and undergoing investigation for CTO recanalization, and conclude with practical perspectives on managing the patient with 1 or more chronic coronary occlusions.

R emarkable progress in the percutaneous management of coronary artery disease has been achieved over the last decade. The scaffolding properties of coronary stents have resulted in percutaneous coronary intervention (PCI) becoming a predictable procedure, with reduced rates of acute closure and late restenosis compared with balloon angioplasty alone. 1,2 More recently, the site-specific delivery of antiproliferative agents from drug-eluting stents has been demonstrated to markedly attenuate vascular responses leading to neointimal hyperplasia, further reducing the occurrence of clinical and angiographic restenosis to Ͻ10% in most patients. 3,4 PCI in patients with acute coronary syndromes and acute myocardial infarction (AMI) has also been proven to save lives, reduce rates of myocardial infarction (MI), and enhance quality of life compared with alternative treatment modalities. [5][6][7] With these advances in perspective, it is often stated that successful recanalization of chronic total occlusions (CTOs) of native coronary arteries represents the "last frontier" of PCI. This statement is made in deference to the fact that CTOs represent the most technically challenging lesion subset that interventional cardiologists face, with procedural success rates considerably lower than those achieved in nonoccluded coronary vessels or acutely occluded arteries. Moreover, no consensus exists with regard to the definition of CTO, the factors related to procedural failure and/or complications, and the optimal technical approach. Indeed, until recently, the clinical benefits of PCI in CTOs had not been demonstrated.An international panel of 47 physicians from 9 countries was therefore convened in New York City for 2 days in January 2004, the purpose of which was to reach consensus on the current state of the art of CTO angioplasty (see Appendix in the online-only Data Supplement for a complete participant list). This goal was approached through a series of didactic lectures, roundtable discussions, breakout focus groups, and the performance of 14 live case demonstrations of CTO angioplasty by many of the world's most skilled operators in this subspecialty. The present report represents a synthesis of the findings from this meeting and also incorporates a literature review from the field of CTO intervention. Topics covered in Part I of this review include definitions, prevalence, and clinical presentation of CTOs; the anatomy and histopathology of coronary occlusions; experimental CTO models; and the clinical relevance and rationale for CTO revascularization. Part II will review the technical approach to and clinical outcomes after percutaneous intervention of CTOs and describe the novel devices and drugs approved and undergoing investigation for CTO recanalization.

In addition to reflecting the degree of frailty, the CFS was a useful marker for predicting late mortality in an elderly transcatheter aortic valve replacement cohort.