Pedro Alves Lemos Neto

Emerging technologies: Polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter

Drug-eluting stents have proven to be effective in reducing the risk of late restenosis. In order to achieve a controlled and prolonged release of the antiproliferative agent, current drug-eluting stents utilise various biodegradable as well as non-erodible polymeric blends to coat the stent surface and to serve as drug carriers. The utilisation of polymeric compounds in current drug-eluting stents may eventually limit their performance as well as their clinical applicability due to the potential induction of undesirable local reactions. The development of alternative, polymer-free drug carriers has the potential to overcome some of the limitations of current drug-eluting stent formulations. Moreover, improvements in drug carriers may also result in an expansion of the technological possibilities for other intravascular drug delivery systems, such as metal-free or even implant-free solutions. This article describes the structure and the preclinical validation profile of a novel phospholipid encapsulated sirolimus nanocarrier, used as a coating in two formulations: a coronary stent-plus-balloon system and a stand-alone balloon catheter. The nanoparticles provided a stable, even and homogenous coating to the devices in both formulations. Dose-finding studies allowed the most appropriate identification of the best nanoparticle structure associated with an extremely efficient transfer of drug to all layers of the vessel wall, achieving high tissue concentrations that persisted days after the application, with low systemic drug leaks.

Effectiveness of the sirolimus-eluting stent in the treatment of patients with a prior history of coronary artery bypass graft surgery

ObjectivePercutaneous coronary intervention in patients with a history of previous coronary artery bypass grafting (CABG) is associated with an increased rate of subsequent adverse events compared to those without prior CABG. We evaluated the impact of utilizing the sirolimus-eluting stent (SES) in this high-risk population. MethodsSince April 2002, SES implantation was utilized as the default strategy for all percutaneous procedures in our hospital. Consecutive patients with a history of previous CABG and de novo lesions (n=47) treated exclusively with SES, were compared to 66 patients who received bare stents in the 6-month period just before SES introduction. ResultsThere were no significant differences between the groups (SES and bare stent) with respect to baseline clinical or lesion characteristics. The only difference between the groups related to the nominal diameter of stent utilized, which was smaller in the SES group than the bare stent group. (The maximum diameter of SES available was 3.0u2009mm). At 1 year, the cumulative incidence of major adverse events (defined as death, myocardial infarction, or target vessel revascularization) was significantly lower in the SES group than the bare stent group [8.5 versus 30.3%, hazard ratio 0.37 (95% confidence interval 0.15–0.91); P=0.03]. ConclusionsThe utilization of the sirolimus-eluting stent for percutaneous intervention in a high-risk population with a history of previous CABG surgery is associated with a significant reduction in the rate of major adverse cardiac events at 1 year.

EuroSCORE II and STS as mortality predictors in patients undergoing TAVI

INTRODUCTIONnthe EuroSCORE II and STS are the most used scores for surgical risk stratification and indication of transcatheter aortic valve implantation (TAVI). However, its role as a tool for mortality prediction in patients undergoing TAVI is still unclear.nnnOBJECTIVEnto evaluate the performance of the EuroSCORE II and STS as predictors of in-hospital and 30-day mortality in patients undergoing TAVI.nnnMETHODSnwe included 59 symptomatic patients with severe aortic stenosis that underwent TAVI between 2010 and 2014. The variables were analyzed using Students t-test and Fishers exact test and the discriminative power was evaluated using receiver operating characteristic curve (ROC) and area under the curve (AUC) with a 95% confidence interval.nnnRESULTSnmean age was 81±7.3 years, 42.3% men. The mean EuroSCORE II was 7.6±7.3 % and STS was 20.7±10.3%. Transfemoral procedure was performed in 88.13%, transapical in 3.38% and transaortic in 8.47%. In-hospital mortality was 10.1% and 30-day mortality was 13.5%. Patients who died had EuroSCORE II and STS higher than the survivors (33.7±16.7vs. 18.6±7.3% p=0,0001 for STS and 13.9±16.1 vs. 4.8±3.8% p=0.0007 for EuroSCORE II). The STS showed an AUC of 0.81 and the EuroSCORE II of 0.77 and there were no differences in the discrimination ability using ROC curves (p=0.72).nnnCONCLUSIONnin this cohort, the STS and EuroSCORE II were predictors of in-hospital and 30-days mortality in patients with severe aortic stenosis undergoing TAVI.

Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction

Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.

Early Removal of the Arterial Sheath After Percutaneous Coronary Intervention Using the Femoral Approach: Safety and Efficacy Study

ABSTRACT Introduction We evaluated the safety and efficacy of protamine administration, guided by activated clotting time, for the immediate femoral arterial sheath removal in patients undergoing percutaneous coronary intervention with unfractionated heparin in order to propose an algorithm for clinical practice. Methods Prospective study with consecutive patients with stable angina or low-to-moderate risk acute coronary syndrome. We compared patients with an early removal of the arterial sheath to those whose sheath removal was based on a standard protocol. Results The early removal group (n = 149) had lower access manipulation time than the conventional group (58.3 ± 21.4 minutes vs. 355.0 ± 62.9 minutes; p p p = 0.49). There was no stent thrombosis during hospitalization and no significant differences in the incidence of major vascular or bleeding events. The incidence of other bleeding events leading to a prolonged in-hospital length of stay was lower in the early removal group (1.3% vs. 5.1%; p = 0.05). Conclusions: The selective use of an approach for immediate femoral sheath removal, based on activated clotting time guidance and protamine administration, is a safe and effective option in patients undergoing percutaneous coronary intervention by femoral access.

Trends in the Use of the Transradial Approach in More Than a Decade: The InCor's Experience

ABSTRACT Background : The use of the radial approach for diagnostic cardiac catheterization and percutaneous coronary interventions varies among different interventional cardiology centers in the world. We describe the trends in the use of this approach over the past 14 years at a tertiary hospital. Methods : Consecutive coronary procedures performed from 1999 to 2013 at a single center, in patients aged ≥ 35 years were identified. Age, gender, resource provider (Public or Private Healthcare System) and the complexity of the procedure (diagnostic or therapeutic) were retrospectively analyzed. Results : 103,253 procedures were included. The Brazilian Public Healthcare Service (SUS – Sistema Unico de Saude ) was the resource provider in 77% of the cases. Mean age of patients was 62.2 ± 11.3 years and 58% were male. The radial approach was used in 6,402 (6.2%) procedures, showing a significant rise over time, which was more evident when analyzed comparatively for the six timepoints of service experience: 0.2%; 0.6%; 3.1%; 2.1%; 6.9%, and 24.4% respectively (p Conclusions : We demonstrated progressive changes in the profile of the use of access routes for diagnostic cardiac catheterization and percutaneous coronary interventions at a large center over time. These data are consistent with the global trend and are significantly robust, especially when the last sextile is analyzed. RESUMO Tendencias da Utilizacao da Via de Acesso Transradiai em Mais de Uma Decada: A Experiencia do InCor Introduco : A utilizacao da via radial para a realizacao de cateterismo cardiaco diagnostico e intervencao coronaria percutânea varia entre os diversos centros de hemodinâmica. Descrevemos as tendencias do uso dessa via de acesso ao longo dos ultimos 14 anos num servico terciario. Metodos : Foram identificados procedimentos coronarianos consecutivos realizados de 1999 a 2013, em um unico centro, em pacientes com idade ≥ 35 anos. Dados como idade, sexo, fonte provedora de recursos (Sistema de Saude Publico ou Saude Suplementar/Privado) e complexidade do procedimento (diagnostico ou terapeutico) foram retrospectivamente analisados. Resultados : Foram incluidos 103.253 procedimentos, dos quais o Sistema Unico de Saude (SUS) foi o provedor de recursos em 77% dos casos. A media de idades dos pacientes foi 62,2 ± 11,3 e 58,8% eram do sexo masculino. A via radial foi utilizada em 6.402 (6,2%) dos procedimentos, apresentando ascenSao significativa ao longo do tempo, mais evidente quando analisada comparativamente nos seis periodos de experiencia do servico: 0,2%, 0,6%, 3,1%, 2,1%, 6,9% e 24,4%, respectivamente (p Conclusoes : Demonstramos a progressiva modificacao do perfil de utilizacao das vias de acesso para a realizacao de cateterismo cardiaco diagnostico e intervencao coronaria percutânea de um centro de grande porte ao longo do tempo. Esses dados sao condizentes com a tendencia mundial e de significativa robustez, principalmente quando analisado o ultimo sextil.

Hemodynamic Effects of Noninvasive Ventilation in Patients with Venocapillary Pulmonary Hypertension

Background The hemodynamic effects of noninvasive ventilation with positive pressure in patients with pulmonary hypertension without left ventricular dysfunction are not clearly established. Objectives Analyze the impact of increasing airway pressure with continuous positive airway pressure on hemodynamic parameters and, in particular, on cardiac output in patients with variable degrees of pulmonary hypertension. Methods The study included 38 patients with pulmonary hypertension caused by mitral stenosis without left ventricular dysfunction or other significant valvulopathy. The hemodynamic state of these patients was analyzed in three conditions: baseline, after continuous positive pressure of 7 cmH2O and, finally, after pressure of 14 cmH2O. Results The population was composed of predominantly young and female individuals with significant elevation in pulmonary arterial pressure (mean systolic pressure of 57 mmHg). Of all variables analyzed, only the right atrial pressure changed across the analyzed moments (from the baseline condition to the pressure of 14 cmH2O there was a change from 8 ± 4 mmHg to 11 ± 3 mmHg, respectively, p = 0.031). Even though there was no variation in mean cardiac output, increased values in pulmonary artery pressure were associated with increased cardiac output. There was no harmful effect or other clinical instability associated with use application of airway pressure. Conclusion In patients with venocapillary pulmonary hypertension without left ventricular dysfunction, cardiac output response was directly associated with the degree of pulmonary hypertension. The application of noninvasive ventilation did not cause complications directly related to the ventilation systems.

CRT-400.01 Training, Simulation and Validation of Therapeutic Hypothermia as an Adjuvant Treatment in St Segment Elevation Myocardial Infarction

Therapeutic hypothermia (TH) reduces the damage by ischemic / reperfusion syndrome in cases of cardiac arrest, in which its application is already widely established and carried out in centers of excellence. However its use in patients with ST segment elevation myocardial infarction (STEMI) is still

Anomalous origin of the right coronary artery from the left sinus of Valsalva: prevalence, clinical characteristics, and long-term follow-up

RESUMO Introducao Anomalias de origem das arterias coronarias sao achados pouco frequentes em pacientes submetidos a cinecoronariografia. Em alguns casos, em seu trajeto, elas podem sofrer compressao extrinseca, ocorrendo isquemia miocardica. O presente estudo teve como objetivo relatar a prevalencia, as caracteristicas clinicas e o impacto prognostico da origem anomala da arteria coronaria direita oriunda do seio de Valsalva esquerdo. Metodos Foi feito um rastreamento nos procedimentos realizados em um servico de cardiologia intervencionista, no periodo entre 1999 e 2012. [...]

CRT-700.06 Safety of Endovascular Therapeutic Hypothermia as an Adjuvant Therapy in Acute ST Segment Elevation Myocardial Infarction

Therapeutic hypothermia (TH) reduces the damage by ischemia and reperfusion cell syndrome in cardiac arrests, in which its application is already widely established and carried out in centers of excellence. However its role in patients with acute ST segment elevation myocardial infarction (STEMI)