Bruno da Silva Matte

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

To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in‐stent restenosis (ISR) in a swine model.

Perfil da intervenção coronária percutânea no infarto agudo do miocárdio com supradesnivelamento do segmento ST no Brasil de 2006 a 2010: registro CENIC

BACKGROUND: Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality. This study aims to outline the national profile of percutaneous coronary intervention (PCI) in the setting of AMI, analyzing different time periods and geographic regions, with focus on primary PCI and adjunctive pharmacological and mechanical treatments. METHODS: Data from 20,004 patients with ST elevation myocardial infarction (STEMI) undergoing PCI and included in the CENIC Registry (National Center of Cardiovascular Interventions) from January 2006 to December 2010 were included in this study. Data were obtained from 252 centers located in 22 states from five different geographic regions in the country. RESULTS: Primary PCI accounted for 57.8% of PCI performed in the setting of AMI, followed by elective PCI after STEMI (35.7%), rescue PCI (6.1%) and facilitated PCI (0.4%). The evolution over time showed a progressive increase in the number of primary PCIs in Brazil, from 56.7% in 2006 to 71.6% in 2010. The mean door-to-balloon time of primary PCI in Brazil during this period was 2 hours. Thrombus aspiration increased from 0.4% in 2006 to 8.2% of cases in 2010. Procedural success rate was 93.8%, while in-hospital mortality was only 2.8%. CONCLUSIONS: PCI in the setting of STEMI has improved from 2006 to 2010, although heterogeneously in the different regions of Brazil, due to increased primary PCI rates and higher use of thrombus aspiration devices, which have not been incorporated in the routine practice. Investments in staff training and implementation of clinical protocols are essential to optimize the door-to-balloon time and improve clinical outcomes.

Safety and Efficacy of Second-Generation Everolimus-Eluting Stents

The second-generation everolimus-eluting stents (EES) are loaded with everolimus, which is a powerful analog of sirolimus; the drug carrier consists of a thin layer of durable and biocompatible fluorocopolymer, and the platform is made of cobalt-chromium alloy to allow thinner struts as well as to enhance stent radial strengh, delivery, and percutaneous coronary intervention success rates. EES are safe and efficient for the treatment of coronary artery disease in a wide range of anatomic settings, where several trials show EES superior to paclitaxel-eluting stents (PES); however, the superiority of EES over sirolimus-eluting stents (SES) is not so clear as over PES. In specific profiles of subjects such as diabetic patients, women, and patients presenting acute myocardial infarction (AMI), EES are also safe and efficient. In diabetic patients, the expected superiority of EES over PES and SES has not been confirmed. EES are equally safe and effective for women as for the general population. In the AMI setting, EES promote safety and efficacy outcomes similar to those found in non-AMI patients, as well as lower stent thrombosis rates in comparison with SES and PES. In conclusion, second-generation EES are safe and efficient for treatment of coronary artery disease in a wide range of anatomic and clinical settings.

Multiple Culprit Coronary Artery Thrombosis in a Patient with Coronary Ectasia

We here report a case of ST-elevation myocardial infarction (STEMI) due to simultaneous acute coronary artery occlusions of two major coronary arteries in a patient with coronary ectasia. The patient had been previously submitted to percutaneous coronary angioplasty with bare metal stent implantation in both culprit vessels. Very late stent thrombosis could be the cause of the first occlusion, triggering the event in the other vessel. In addition, concomitant embolic sources were not identified. Although routine aspiration thrombectomy in STEMI was not proven to be beneficial in randomized clinical trials, it was of great value in this case. We also discuss the relation between coronary ectasia, chronic inflammatory status, and increased platelet activity which may have caused plaque disruption in another already vulnerable vessel.

Reply to “Predictable Superiority of Everolimus-Eluting Stent Over Paclitaxel-Eluting Balloon in Patients with In-Stent Restenosis”

Predictable Superiority of Everolimus-Eluting Stent Over Paclitaxel-Eluting Balloon in Patients With In-Stent Restenosis We read with great interest the study performed by Alfonso et al comparing the efficacy of everolimus-eluting stents (EES) and drug-eluting balloons (DEB) in patients with in-stent restenosis (ISR). We appreciate their findings; however, we would like to discuss some issues. In fact, the comparison was between EES and paclitaxel-eluting balloon (PEB). Being so, 2 subjects were compared, that is, 2 different devices (drug-eluting balloon vs drugeluting stent) and 2 different drugs (everolimus vs paclitaxel). Several studies comparing EES and paclitaxel-eluting stent (PES) showed the superiority of EES over PES in a wide range of anatomic settings, such as de novo lesions, multivessel disease, small vessels, saphenous vein graft, and chronic total occlusion. Regarding ISR treatment, there are only a few data from small trials related to the comparison between EES and PES in this setting. Almalla et al demonstrated that EES resulted in significant reduced rates of target lesion revascularization compared with PES for the treatment of bare metal stent restenosis at 1-year follow-up, which is the same follow-up period of the study under discussion. Hence, the literature data support EES superiority over PES, mainly driven by the higher efficacy of everolimus over paclitaxel in the inhibition of smooth muscle cells proliferation, that is, the physiopathologic basis of ISR. This paclitaxel inferiority led to the PES replacement by drug-eluting stents releasing sirolimus or its analogs, such as EES, in the current clinical practice. Therefore, the superiority of EES over paclitaxel-eluting balloon in the treatment of patients with ISR demonstrated by Alfonso et al was predictable. Our group showed potential benefits of sirolimus nanoparticles for the treatment of ISR in an experimental study through the significant neointima reduction achieved by the strategy

Associação entre remodelamento vascular e núcleo necrótico em artérias coronárias: análise por ultrassom intracoronário com Histologia Virtual®

BACKGROUND: Anatomopathological studies suggest an association of positive vascular remodeling and vulnerable coronary plaques. The objective of this study was to verify whether there is a correlation between positive vascular remodeling and necrotic core in atherosclerotic coronary lesions. METHODS: We studied 270 cross sections obtained by Virtual Histology® in 30 patients who had positive remodeling in coronary artery segments with lesions > 50%, identified by coronary angiography. Seven cross sections were assessed per segment of coronary artery, including the cross section with the highest remodeling index, denominated cross section of interest (cross section 4). RESULTS: Mean age was 60.8 ± 8.8 years, 80% were male and 30% were diabetic. Unstable angina was the most frequent clinical presentation (56.6%) and the left anterior descending artery was the most analyzed vessel (43%). The vessel reference area was 15.5 ± 4.9 mm² and the remodeling index in cross section 4 was 1.2 ± 0.1. Repeated measures analysis of variance showed a higher percentage of necrotic core in the cross section of interest (P < 0.001). We observed a positive correlation of coronary artery remodeling and necrotic core (r = 0.79; P < 0.001). CONCLUSIONS: Positive coronary artery remodeling is associated to the presence of necrotic core, which characterizes vulnerable atherosclerotic plaques. The search for positive arterial remodeling may be a useful strategy for detecting vulnerable plaques before rupture.

Identificação de genes envolvidos na síntese de proteínas de células musculares lisas com expressão aumentada em placas ateromatosas associados a hiperplasia neointimal após implante de stents não-farmacológicos: estudo GENESIS-R

BACKGROUND: Coronary restenosis is a poorly understood phenomenon that remains a challenge even in the drug-eluting stent era. This study is aimed at identifying the genes involved in structural and functional protein synthesis of smooth muscle cells with increased expression in human atheromatous plaques associated to neointimal hyperplasia after bare-metal stent implantation. METHODS: Atheromatous plaques were obtained by directional atherectomy prior to stenting. Gene expression analysis was performed using the Affymetrix GeneChip system. Patients were submitted to intravascular ultrasound 6 months after the procedure for in-stent volumetric analysis. We evaluated the correlation between gene expression in atheromatous plaques and the percentage of in-stent intimal hyperplasia. RESULTS: Most patients were male (85.7%), with 60.2 ± 11.4 years of age, 35.7% were diabetic and the percentage of in-stent intimal hyperplasia was 29.9 ± 18.7%. There was no change in the percentage of in-stent intimal hyperplasia in patients with or without diabetes (29.5% vs. 30.7%; P = 0.89). There was no correlation between stent length and the percentage of in-stent intimal hyperplasia (r = -0.26; P = 0.26) or between stent diameter and the percentage of in-stent intimal hyperplasia (r = 0.14; P = 0.56). Eight genes related to smooth muscle cell structural and functional protein synthesis had a positive correlation with the percentage of in-stent intimal hyperplasia. CONCLUSIONS: De novo coronary lesions show increased expression of genes related to smooth muscle cell structural and functional protein synthesis associated to future significant in-stent neointimal hyperplasia, emerging as novel therapeutic targets.