Long-term outcomes of drug-eluting versus bare-metal stent implantation in patients with chronic total coronary artery occlusions.

BACKGROUND: There are limited data on the efficacy of drug-eluting stents (DES) for treatment of chronic total occlusions (CTO). The aim of the study was to evaluate the long-term clinical outcomes of DES implantation for CTO compared with bare-metal stent (BMS) implantation. METHODS: Between June 1995 and December 2006, a total of 1184 patients with successful recanalization of at least one de novo CTO lesion were consecutively registered, including 660 (55.7%) who underwent DES and 524 (44.3%) who underwent BMS implantation. All patients were followed up for up to 5 years for occurrence of major adverse cardiac events (MACE). Long-term survival rates were estimated with the Kaplan-Meier method. RESULTS: Baseline clinical and angiographic characteristics were comparable between the two groups except that patients in the DES group received longer dual antiplatelet therapy ((7.4 +/- 2.5) months vs (1.7 +/- 0.8) months, P < 0.001). Average follow-up periods were (4.7 +/- 0.89) and (3.2 +/- 1.3) years for the BMS and DES groups, respectively. There was no significant difference in 5-year survival rates between the two groups (90.3% for DES group vs 89.6% for BMS group, Log-rank P = 0.38), but the 5-year target vessel revascularization (TVR)-free survival rate in the DES group was significantly higher than that in the BMS group (81.6% vs 73.5%, Log-rank P < 0.001). The cumulative MACE-free survival in the DES group was also significantly higher than that in the BMS group (80.6% vs 71.5%, Log-rank P < 0.001). The rates of re-admission caused by cardiovascular disease (27.0% vs 37.8%, P < 0.001) and the need for bypass surgery were significantly lower in the DES group (1.5% vs 3.4%, P < 0.05). By multivariable analysis, DES implantation could significantly lower the long-term MACE risk of PCI for CTO patients (HR: 0.492; 95% CI 0.396 - 0.656, P < 0.001). Left ventricular ejection fraction < 50% and elderly (> or = 65 years) were identified as independent predictors of long-term MACE during follow-up. CONCLUSION: This study demonstrates the long-term (up to 5 years) efficacy of DES for treatment of CTO, which is superior to BMS implantation in reducing the rates of TVR and MACE, as well as the need of re-admission and bypass surgery.

[Long-term clinical outcomes of patients undergoing successful or failed percutaneous coronary intervention for chronic total occlusions of coronary arteries].

OBJECTIVE: To evaluate the long-term outcomes of successful or failed revascularization in patients with chronic total occlusions (CTO). METHODS: The clinical data of 1332 consecutive patients underwent percutaneous coronary intervention (PCI) for CTO between June 1993 and December 2006 in our hospital were analyzed. These patients were divided into two groups according to the procedural success (n = 1202) or failure (n = 130). RESULTS: Overall success rate of procedure was 90.2% (1202/1332). The patients in CTO success group experienced a superior 10-year survival rate (76.9% vs. 64.6%, log rank P = 0.012) and a significantly higher no major adverse cardiovascular event (MACE) survival rate (41.8% vs. 27.6%, log rank P < 0.001) compared to the patients in CTO failure group. During the long-term follow-up, the proportion of patients who accepted coronary artery bypass grafting (CABG) was significantly lower in CTO success group than that in the CTO failure group (4.3% vs. 14.6%, P < 0.001). CONCLUSION: Successful PCI procedure leads to increased long-term survival and MACE-free survival and the reduced need for CABG for patients with CTO lesions.

Heat shock protein 70 interacts with aquaporin-2 and regulates its trafficking.

The trafficking of aquaporin-2 (AQP2) involves multiple complex pathways, including regulated, cAMP-, and cGMP-mediated pathways, as well as a constitutive recycling pathway. Although several accessory proteins have been indirectly implicated in AQP2 recycling, the direct protein-protein interactions that regulate this process remain largely unknown. Using yeast two-hybrid screening of a human kidney cDNA library, we have identified the 70-kDa heat shock proteins as AQP2-interacting proteins. Interaction was confirmed by mass spectrometry of proteins pulled down from rat kidney papilla extract using a GST-AQP2 C-terminal fusion protein (GST-A2C) as a bait, by co-immunoprecipitation (IP) assays, and by direct binding assays using purified hsc70 and the GST-A2C. The direct interaction of AQP2 with hsc70 is partially inhibited by ATP, and the Ser-256 residue in the AQP2 C terminus is important for this direct interaction. Vasopressin stimulation in cells enhances the interaction of hsc70 with AQP2 in IP assays, and vasopressin stimulation in vivo induces an increased co-localization of hsc70 and AQP2 on the apical membrane of principal cells in rat kidney collecting ducts. Functional knockdown of hsc70 activity in AQP2 expressing cells results in membrane accumulation of AQP2 and reduced endocytosis of rhodamine-transferrin. Our data also show that AQP2 interacts with hsp70 in multiple in vitro binding assays. Finally, in addition to hsc70 and hsp70, AQP2 interacts with several other key components of the endocytotic machinery in co-IP assays, including clathrin, dynamin, and AP2. To summarize, we have identified the 70-kDa heat shock proteins as a AQP2 interactors and have shown for hsc70 that this interaction is involved in AQP2 trafficking.