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Abstract: Postangioplasty restenosis is a multifactorial process and involves mechanisms such as inflammation and stimulation of the expression of growth factors. Lipoprotein-associated phospholipase A2 (Lp-PLA2) can modify inflammatory responses by hydrolyzing phospholipids with shortened and/or oxidized sn-2 residues. In this study, we tested a hypothesis that adenovirus-mediated Lp-PLA2 gene transfer can reduce restenosis in rabbits. Aortas of cholesterol-fed NZW rabbits were balloon-denuded and intra-arterial gene transfer was performed using Dispatch catheter with Lp-PLA2 or LacZ adenoviruses (1.15×1010 pfu). Intima/media ratio (I/M), histology and cell proliferation were analyzed. Two weeks after the gene transfer I/M in the LacZ-transduced control group was 0.45±0.05 but Lp-PLA2 gene transfer reduced I/M to 0.25±0.03. At four weeks time point I/M in the Lp-PLA2 group (0.34±0.05) was also lower than in the LacZ group (0.53±0.06). Plasma Lp-PLA2 activity was increased in the Lp-PLA2 group (48.2±4.2) as compared to the LacZ group (33.6±3.51) at two weeks time point. Transgene expression was detected in the arterial wall two and four weeks after the procedure. Apoptosis was higher in the control vessels than in the Lp-PLA2 group at two weeks time point. In conclusion, local adenovirus-mediated Lp-PLA2 gene transfer resulted in a significant reduction in neointima formation in balloon-denuded rabbit aorta and may be useful for the prevention of restenosis after arterial manipulations. [Copyright &y& Elsevier]

Background: Rates and importance of periprocedural myocardial injury (PMI) after crossing coronary chronic total occlusions (CTOs) is not well understood. This study sought to investigate long-term clinical implications of PMI in patients undergoing percutaneous coronary intervention (PCI) for single CTO utilizing antegrade technique., Methods: Out of 11,957 patients undergoing non-urgent PCI, a total of 1110 patients with symptomatic angina and single CTO were treated by antegrade PCI and observed for up to 10 years. The primary objective included cardiac death, while the secondary aim comprised all major adverse cardiovascular and cerebrovascular event (MACCE) rate., Results: Troponin-defined PMI occurred in 4.7% patients (n = 52). At 1 year, the cardiac death and MACCE rates were significantly higher in patients with vs without PMI (hazard ratio [HR], 5.72; 95% confidence interval [CI], 1.59-20.49; P=.01; HR, 1.84; 95% CI, 1.07-3.18; P=.03, respectively). At long-term follow-up, patients with PMI had a trend toward a higher incidence of cardiac death than patients without PMI (HR, 2.51; 95% CI, 0.99-6.33; P=.05) and no differences were demonstrated in terms of overall MACCE between both groups (HR, 1.19; 95% CI, 0.73-1.93; P=.49). After propensity score adjustment, no significant differences were observed regarding the short-term and long-term outcomes., Conclusion: CTO-PCI is a safe procedure if routinely performed in symptomatic patients at a high-volume center. PMI does not influence long-term outcomes after antegrade CTO-PCI.

Background: The performance of second-generation drug-eluting stent (DES) versus first-generation DES implantation in patients with stable angina and single chronic total occlusion (CTO) has not yet been studied. Herein, we sought to investigate whether a successful percutaneous coronary intervention (PCI) for CTO using second-generation versus first-generation polymer-coated DES improved outcomes in a setting of isolated CTO., Methods: Among 7765 patients undergoing elective PCIs between 2006 and 2011, a total of 742 single CTOs were identified. Of these, 496 had a successful PCI and 193 were implanted with DESs. The major adverse cardiovascular event (MACE) records were extracted from the national administrative database and all patients were linked to the 2-year follow-up., Results: When compared to first-generation DES implantation, second-generation implantation once significantly reduced risk of MACE, both at 1-year (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.06-0.36; P=.01) and 2-year follow-up (HR, 0.27; 95% CI, 0.13-0.56; P=.01). The symptom-driven target lesion revascularization (TLR) also occurred less frequently in patients with second-generation DES vs first-generation DES within 2 years of follow-up (HR, 0.15; 95% CI, 0.05-0.44; P=.03). The substantial 2-year benefit of second-generation DES over first-generation DES also persisted after incorporating a propensity score analysis for MACE (HR, 0.24; 95% CI, 0.08-0.72; P=.01) and TLR (HR, 0.15; 95% CI, 0.05-0.49; P=.04)., Conclusions: Successful PCI for CTO using thin-strut polymer-coated DES vs early-generation DES implantation improves outcomes after recanalization of isolated CTO in a setting of stable angina.

Background: There are limited data on the long-term safety and efficacy of drug-eluting stents (DES) implantation in patients with stable angina referred for elective percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). We therefore aim to investigate whether DES compared with bare-metal stent (BMS) implantation improves long-term outcomes after successful recanalization of single CTO., Methods: A total of 345 consecutive patients who underwent successful recanalization of single CTO and received DES or BMS in the Cardioangiology Laboratories of the Medical University of Gdansk between January 1, 2006 and December 31, 2010 were included in the CTO Registry database. We compared the 1-year and long-term clinical outcomes of 137 consecutive patients who underwent PCI for CTO and DES implantation with outcomes of 208 patients after successful CTO treatment with BMS implantation. The median follow-up was 22.6 ± 3 months (21.0 ± 3.9 months for DES vs 23.6 ± 1.5 months for BMS; P<.001). The primary endpoints included a composite of all-cause death and non-fatal myocardial infarction (MI) and composite safety endpoint of major adverse cardiovascular events (MACEs), including death, MI and symptom-driven target lesion revascularization (TLR). A secondary endpoint was a symptom-driven TLR., Results: After stent implantation we noted lower rates of the composite endpoint at 1-year (9.5% DES vs 18.3% BMS; P=.01) and long-term follow-up (11.7% DES vs 21.1% BMS; P=.02) due to fewer episodes of TLR in the DES group (5.1% DES vs 14.4% BMS; P=.006 at 1-year follow-up; 7.3% DES vs 14.4% BMS; P=.04 at long-term follow-up). No significant differences were documented in the rate of death, MI, or in-stent thrombosis between investigated subsets. After adjusting for patient and procedural characteristics as well as propensity, BMS implantation remained independently associated with an increased hazard of 1-year MACE (adjusted hazard ratio [AHR], 2.09; 95% confidence interval [CI], 1.2-3.64; P=.005) and long-term MACEs (AHR, 1.99; 95% CI, 1.18-3.38; P<.01)., Conclusions: DES implantation during PCI for single CTO reduces MACE rate at 1-year and long-term follow-up due to the significant reduction of TLR in the DES group. Therefore, DES implantation should be preferred as an optimal treatment strategy of single CTO in stable angina patients.

Network models have been used to capture, represent and analyse characteristics of living organisms and general properties of complex systems. The use of network representations in the characterization of time series complexity is a relatively new but quickly developing branch of time series analysis. In particular, beat-to-beat heart rate variability can be mapped out in a network of RR-increments, which is a directed and weighted graph with vertices representing RR-increments and the edges of which correspond to subsequent increments. We evaluate entropy measures selected from these network representations in records of healthy subjects and heart transplant patients, and provide an interpretation of the results.

Background: Vein graft stenosis is a common problem after bypass surgery. Vein grafts are ideal targets for gene therapy because transduction can be made ex vivo before grafting. Since chemokines and inflammatory factors are involved in vein graft thickening, we tested a hypothesis that the vaccinia virus anti-inflammatory protein 35K which can sequester CC-chemokines, can reduce vein graft thickening in vivo., Materials and Methods: We used adenovirus-mediated gene transfer (1x10(9) pfu/ml) of 35K and compared its effects on reducing stenosis in a rabbit jugular vein graft model with tissue inhibitor of metalloproteinase-1 (TIMP-1) and LacZ control gene. TIMP-1 was used in this study because it has previously been shown to inhibit vein graft stenosis in other model systems. The expression of transgenes in the transduced segments was confirmed by RT-PCR. Vein grafts were analyzed using immunohistological and morphometric methods at the three-day time-point and at two-week and four-week time-points., Results: It was found that the anti-inflammatory protein 35K was an efficient factor in reducing neointima formation at the two-week time-point, indicating that inflammatory factors play an important role in vein graft stenosis. At the four-week time-point, 35K still showed a reduced accumulation of macrophages. TIMP-1 also tended to reduce neointimal thickening at the two-week time-point as compared to LacZ., Conclusion: It was found that 35K is an efficient factor in reducing neointima formation, macrophage accumulation and proliferation in rabbit vein grafts after adenoviral ex vivo gene transfer.

Previous studies have shown that fibroblast growth factor (FGF)-1, FGF-2, and FGF-5 induce therapeutic angiogenesis. Here, we investigated the potential of FGF-4 for therapeutic neovascularization in comparison to vascular endothelial growth factor (VEGF), using adenoviral gene transfer in a novel rabbit hind limb ischemia model, with ischemia restricted to the calf. Magnetic resonance imaging and a modified Miles assay showed that both AdFGF-4 and AdVEGF given intramuscularly (i.m.) resulted in increases in vascular permeability and edema in transduced muscles 6 days after the gene transfer. In contrast, recombinant FGF-4 protein injected in the rabbit skin did not induce acute vascular permeability. Injections (i.m.) of AdFGF-4 and AdVEGF, but not intra-arterially administered AdVEGF, increased collateral growth, popliteal blood flow, and muscle perfusion compared with controls. The angiogenesis response consisted mainly of the enlargement of pre-existing vessels rather than an increase in capillary density. Adenoviral FGF-4 overexpression up-regulated endogenous VEGF, which may explain many of the effects thought to be specific for VEGF such as the increase in vascular permeability. This study demonstrates for the first time that FGF-4 induces vascular permeability, therapeutic angiogenesis, and arteriogenesis comparable to that of VEGF and could be useful for the treatment of peripheral vascular disease.