Background:With aging population, the prevalence and incidence of heart failure (HF) have been increasing worldwide. However, the characteristics and outcomes of patients with HF in an era of aging are not well established in Japan. Methods and Results:The Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter, nationwide registry, was designed to study the clinical characteristics and outcomes of patients hospitalized with HF throughout Japan in 2013. One-hundred and twenty-eight hospitals were selected by cluster random sampling and 13,238 hospitalized patients with HF were identified by medical record review. Demographics, medical history, severity, treatment, and in-hospital and long-term outcome data were collected from the Diagnostic Procedure Combination and medical charts. Data were analyzed using univariate and multivariate logistic regression analysis. The mean age of registered patients was 78.0±12.5 years and 52.8% were male. Elderly patients (age >75 years) accounted for 68.9%, and HF with preserved ejection fraction (HFpEF) accounted for 45.1%. Median length of hospital stay was 18 days and in-hospital mortality was 7.7%. The median follow-up period was 4.3 years, and the incidence rates for cardiovascular death and rehospitalization for HF were 7.1 and 21.1 per 100 person-years, respectively. Conclusions:A contemporary nationwide registry demonstrated that hospitalized HF patients were very elderly, HFpEF was common, and their prognosis was still poor in Japan.

Objective-We have previously shown that the intramuscular transfer of the anti-monocyte chemoattractant protein-1 (MCP-1) gene (called 7ND) is able to prevent experimental restenosis. The aim of this study was to determine the in vivo efficacy and safety of local delivery of 7ND gene via the gene-eluting stent in reducing in-stent neointima formation in rabbits and in cynomolgus monkeys. Methods and Results-We here found that in vitro, 7ND effectively inhibited the chemotaxis of mononuclear leukocytes and also inhibited the proliferation/migration of vascular smooth muscle cells. We then coated stents with a biocompatible polymer containing a plasmid bearing the 7ND gene, and deployed these stents in the iliac arteries of rabbits and monkeys. 7ND gene-eluting stents attenuated stent-associated monocyte infiltration and neointima formation after one month in rabbits, and showed long-term inhibitory effects on neointima formation when assessments were carried out at 1, 3, and 6 months in monkeys. Key Words: restenosis Ⅲ inflammation Ⅲ leukocytes Ⅲ stents Ⅲ smooth muscle cells T he use of polymer-coated drug-eluting stents (DES) for local drug delivery has proved to be a useful strategy for the prevention of restenosis. 1-3 However, recent clinical reports raise the possibility of a risk of stent thrombosis in DES compared with bare metal stent. 4 -6 Drugs released from first-generation DES (sirolimus or paclitaxel) exert distinct biological effects 3,4 : although primarily aimed to prevent vascular smooth muscle cell (VSMC) proliferation, which is one of central factors in the pathogenesis of restenosis, they also impair reendothelialization, which leads to delayed arterial healing and thrombogenesis. The use of sirolimuseluting stents in a porcine model was associated with no apparent long-term effects and with the delayed inflammation and proliferation. 7,8 In human pathologic study with 40 patients who died after the currently-approved DES implantation, it was suggested that the DES caused a persistent fibrin deposition and delayed reendothelialization compared with bare metal stent implantation. 9 Therefore, the development of a novel DES system with less adverse effects is needed. Conclusions-StrategyWe have recently devised a new gene therapy strategy for the delivery of the anti-monocyte chemoattractant protein-1 (MCP-1) in which plasmid cDNA encoding a mutant MCP-1 gene is transfected into skeletal muscle. 10 This mutant MCP-1 protein, called 7ND, lacks the N-terminal amino acids 2 through 8 and has been shown to function as a dominantnegative inhibitor of MCP-1. Using this systemic gene transfer strategy, we have demonstrated that blocking MCP-1-derived signals reduced neointima formation after balloonand stent-induced injury 11-14 and atherosclerosis 15,16 in animals, including nonhuman primates. Overall, these data suggest that an antiinflammatory strategy targeting MCP-1 may be an appropriate and reasonable approach for the prevention of restenosis.Local delivery of 7ND through a gene-eluting stent ma...

Background-Nuclear factor-B (NF-B) plays a critical role in the vascular response to injury. However, the role of NF-B in the mechanism of in-stent restenosis remains unclear. We therefore tested the hypothesis that blockade of NF-B by stent-based delivery of a cis-element "decoy" of NF-B reduces in-stent neointimal formation. Methods and Results-Stents were coated with a polymer containing or not containing NF-B decoy, which represented a fast-release formulation (Ͻ7 days). Bare, polymer-coated, and NF-B decoy-eluting stents were implanted in iliac arteries of hypercholesterolemic rabbits. Increased NF-B activity was noted at early stages after stenting, which was suppressed by stent-based delivery of NF-B decoy. NF-B decoy-eluting stents also reduced monocyte infiltration and monocyte chemoattractant protein-1 expression and suppressed CD14 activation on circulating leukocytes. Importantly, NF-B decoy-eluting stents attenuated neointimal formation on day 28. There was no evidence of an incomplete healing process (persistent inflammation, hemorrhage, fibrin deposition, impaired endothelial regeneration) at the site of NF-B decoy-eluting stents. Transfection of NF-B decoy suppressed proliferation of human coronary artery smooth muscle cells in vitro. No systemic adverse effects of NF-B decoy were detected. Conclusions-Stent-based local delivery of NF-B decoy reduced in-stent neointimal formation with no evidence of incomplete healing. These data suggest that this strategy may be a practical and promising means for prevention of in-stent restenosis in humans.