Safety and mid-term outcome of endovascular therapy for internal carotid artery disease: a 15-year experience at a single-centre angiology institution.

BACKGROUND: Endovascular therapy of carotid artery disease has emerged as a potential alternative to endarterectomy and its clinical practise dramatically increased in many parts of the world. This study aims to determine the safety and mid-term outcome of carotid artery stenting (CAS) within a 15-year carotid program at a single-centre institution. PATIENTS AND METHODS: We retrospectively analysed all CAS-procedures performed at our institution between 1995 and 2009. RESULTS: During the observation period, a total of 497 CAS procedures were attempted in 460 patients with stenoses of the internal carotid artery of which 187 (37.6 %) were symptomatic and 310 (62.4 %) were asymptomatic. CAS was successful in 479 (96.4 %) cases and success rate significantly increased throughout the study (p < 0.001). The periprocedural complication rate for death, stroke, and transient ischemic attack (TIA) was 0.4 %, 1.2 %, and 2.6 %, respectively, and the cumulative event rate did not differ between symptomatic and asymptomatic patients (4.8 % vs. 3.9 %; p = 0.62). Age was the only significant predictor for the occurrence of any periprocedural adverse event (OR 2.08 [1.22 - 3.54]; p = 0.007). During a median follow-up of 24 [1; 141] months, the rate of stroke, TIA, and in-stent restenosis was 1.0 %, 2.2 %, and 2.7 %, respectively. CONCLUSIONS: Data from this large observation in everyday clinical patients demonstrate that endovascular therapy in carotid artery disease can be performed safely and with mid-term outcomes comparable to carotid endarterectomy.

A comprehensive approach to visual and functional assessment of experimental vascular lesions in vivo.

The rat carotid injury model is the most widely used model to study the pathophysiology of neointimal hyperplasia as well as the value of novel therapeutic approaches to limit vasoproliferative diseases such as restenosis. For lesion assessment, the current gold standard of histomorphometry neither provides integral insight into the vascular lesion in vivo nor assesses of functional lesion-associated flow alterations and the time course of lesion development. To overcome these limitations, we applied and validated duplex sonography as a novel tool for comprehensive lesions assessment in vivo. Left rat common carotid arteries (CCA) were balloon injured. Duplex sonography was performed in both injured and noninjured CCAs before and up to 14 days postinjury. Sham-operated animals served as controls. The parameters determined were vessel lumen diameter as well as systolic and end-diastolic flow velocity, time-dependent lesion development, and intra- and interobserver variability. Subsequently, the model was applied to validate the therapeutic effect of gene transfer into the vessel wall and compared with histomorphometry. We show that duplex sonography in the experimental carotid injury model allows accurate follow-up of lesion development in vivo with low intra- and interobserver variability. It can be easily adopted to assess the efficacy of therapeutic approaches even with limited technical experience and adds valuable functional data to mere postmortem histomorphometric analysis, thereby closing the gap between experimental approaches and clinical importance of vascular lesions.

A central role of interferon regulatory factor-1 for the limitation of neointimal hyperplasia.

Neointima formation, the leading cause of restenosis after catheter angioplasty, is a paradigm for vascular proliferative responses. Neointima formation is self-limiting after a variable degree of tissue growth, causing significant renarrowing in a substantial number of patients. To investigate the mechanisms that limit neointima formation we studied the role of the transcription factor IRF-1, which is a regulator of interferons and a tumor suppressor. We demonstrate that IRF-1 is highly regulated in human vascular lesions and exhibits a growth inhibitory function in coronary artery smooth muscle cells (CASMC). IRF-1 deficient mice display a high grade of susceptibility towards neointima formation following vessel injury. IRF-1 leads to G(1) cell cycle arrest in CASMC and induces the CDK inhibitor p21. In addition, IRF-1 induces NO production, which is known to attenuate endothelial dysfunction. Mitogen-mediated cellular migration is abrogated by IRF-1. In conclusion, IRF-1 displays pleiotropic anti-restenotic activities in vascular restenosis through transcriptional activation of several relevant mechanisms that limit neointima formation. These findings suggest an important role of this transcription factor as an endogenous inhibitor of neointimal growth following vessel injury and it is likely that IRF-1 regulation also plays a role in the pathophysiology of primary atherosclerosis. In addition, IRF-1 may be an interesting target for interventions to prevent neointimal hyperplasia.