Local delivery of sirolimus nanoparticles for the treatment of in-stent restenosis.

OBJECTIVES: To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model. BACKGROUND: Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high. METHODS: Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment. RESULTS: There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1. CONCLUSIONS: PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.

First-in-man study of simvastatin-eluting stent in de novo coronary lesions: the SIMVASTENT study.

BACKGROUND: Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. METHODS AND RESULTS: Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. CONCLUSIONS: In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

Efeitos agudos do mononitrato de isosorbitol sobre a circulação e isquemia miocárdica em pacientes com aterosclerose coronária / Acute Effects of Isosorbide Mononitrate on Circulation and the Ischemic Myocardium in Patients with Coronary Artery Disease

PURPOSE--To evaluate the acute effects of isosorbide mononitrate on circulation, cardiac function and left ventricular segmental motility in patients with isquemic heart disease due to coronary artery disease. METHODS--Twenty-four patients with ischemic heart disease, 10 women, with mean age of 58 years, were studied during cardiac catheterization, at baseline condition and 5min after intravenous infusion of 0.3mg/kg of isosorbide mononitrate. RESULTS--After infusion of isosorbide mononitrate there were significant reduction in mean right atrial pressure no mean pulmonary artery pressure (< 0.0001), left ventricular and diastolic pressure (p < 0.004), left ventricular systolic pressure (p < 0.002), maximum (p < 0.002) and mean (p < 0.008) aortic pressure, and left ventricular systolic volume (p < 0.004), as well as significant increase in the left ventricular ejection fraction (p < 0.001) and mean velocity of circunferential fibers shortening (p < 0.001). There was no significant modification of minimum aortic pressure, heart rate, cardiac output nor of left ventricular and diastolic volume. With respect of segmental motility of the left ventricle after medication, 38 kypokinetic segments normalized their motility, 4 akinetic segments remained intact, and of the 21 dyskinetic segments, 6 normalized, 8 became hypokinetic and 7 remained dyskinetic. CONCLUSION--Isosorbide mononitrate, when used as intravenous infusion, have a rapid and direct effect on systemic and pulmonary circulation, and improving segmental motility and left ventricular performance in patients with impaired left ventricular motility caused by ischemic heart disease.

Objetivo − Avaliar, durante estudo hemodinâmico e cineangiocardiográfico, os efeitos agudos do mononitrato de isosorbitol, via sistêmica, sobre a circulação e presença de áreas viáveis de isquemia miocárdica, em portadores de cardiopatia isquêmica por aterosclerose coronária obstrutiva. Métodos −Foram estudados, durante estudo hemodinâmico e cineangiocardiográfico, 24 pacientes, 10 mulheres, com média de idade de 58 anos, portadores de cardiopatia isquêmica, em condições basais e 5min após infusão de 0,3mg/kg/peso de mononitrato de isosorbitol por via venosa, para avaliar os efeitos do medicamento sobre a circulação, o desempenho cardíaco e a motilidade segmentar do ventrículo esquerdo (VE). Resultados −Após o uso do medicamento, constatou-se redução significante da pressão média do átrio direito (p<0,01), da pressão média na artéria pulmonar (p<0,000), da pressão sistólica do VE (p<0,002), da pressão diastólica final do VE (p<0,0004), da pressão aórtica máxima (p<0,002), da pressão aórtica média (p<0,008), do volume sistólico final do VE (p<0,004) e aumento da fração de ejeção do VE (p<0,001) e da velocidade média do encurtamento circunferencial (p<0,001). Não houve modificação significante da pressão aórtica mínima, da freqüência cardíaca, do débito cardíaco e do volume diastólico final do VE. Quanto ao comportamento da motilidade segmentar, após o uso do medicamento, os 38 segmentos hipocinéticos normalizaram sua motilidade, os 4 segmentos acinéticos não se alteraram e, dos 21 segmentos discinéticos, 6 normalizaram, 8 se tornaram hipocinéticos e 7 não alteraram sua motilidade segmentar. Constatou-se ainda que o medicamento desenvolveu ação efetiva sobre a circulação, 30s após sua infusão. Conclusão − O mononitrato de isosorbide produziu ação rápida e efetiva sobre a circulação, a motilidade segmentar e desempenho do VE, identificando áreas viáveis com isquemia miocárdica