Natália António

Stimulation of endothelial progenitor cells: a new putative effect of several cardiovascular drugs

The role of vascular endothelium in cardiovascular disorders is well recognized. Mature endothelial cells contribute to the repair of endothelial injury, but they only have a limited capacity to do so. This has led to growing interest and further investigation into circulating endothelial progenitor cells (EPCs) and their role in vascular healing, repair, and postnatal neovascularization. The current perception of vascular health is that of a balance between ongoing injury and resultant vascular repair, mediated at least in part by circulating EPCs. Circulating EPCs play an important role in accelerating endothelialization at areas of vascular damage, and EPC enumeration is a viable strategy for assessing reparative capacity. Recent studies have shown that EPCs are affected both in number and function by several cardiovascular risk factors as well as various cardiovascular disease states, such as hypertension, hypercholesterolemia, and coronary artery disease. The present review summarizes the most relevant studies on the effects of cardiovascular drugs on vascular function and EPCs, focusing on their mechanisms of action.

Endothelial progenitor cells in diabetic patients with myocardial infarction – Can statins improve their function?

The effect of statins on endothelial progenitor cells (EPCs) function derived from diabetic patients (DMpts) with acute myocardial infarction (AMI) is unknown. In this study we assess the response of early and late EPCs from diabetic versus non-diabetic patients (NDMpts) with AMI to statins. EPCs were obtained from 10 diabetic and 10 age-matched non-diabetic male patients with AMI. For each patient, cultures of early and late EPCs were performed under 4 different conditions: normal glucose concentration (control); high glucose concentration; normal glucose concentration with atorvastatin supplementation and normal glucose concentration with pravastatin supplementation. To compare the effect of these treatments on EPC function in DMpts versus NDMpts, we performed in vitro: EPC colony-forming units (CFU) assay; cell cycle analysis; viability assessment and expression of the surface markers CXCR4, CD133, CD34 and KDR. Under control conditions, CFU numbers were reduced in DMpts-derived EPCs when compared to those of NDMpts (1.4±0.8 vs 2.6±1.2 CFU/well, P=0.021). When early EPCs from DMpts were cultured in the presence of statins, CFU capacity was restored, surmounting that of NDMpts under control conditions. Statins significantly improved viability of early EPCs and delayed the onset of late EPCs senescence, even in cells from DMpts. In addition, statins induced approximately a 2-fold increase in the proportion of late EPCs in S-phase of the cell cycle (P<0.05). Statins have a beneficial effect on both early and late EPCs from DMpts with AMI. Despite the functional impairment of EPCs from DMpts, they exhibit similar responsiveness to statins as equivalent cells from NDMpts.

Cardiac resynchronization therapy in the elderly: a realistic option for an increasing population?

Cardiac resynchronization therapy (CRT) has become a mainstay of heart failure treatment. Since heart failure is a disease primarily affecting older patients it is important to evaluate the performance of CRT in this population. Elderly has been suggested as a subgroup less likely to benefit from CRT. This is an important issue that should be clarified, because most patients with heart failure are old. The present review discusses the available data concerning cardiac resynchronization therapy in the elderly, focusing on efficacy, indication, safety, and impact of co-morbidities.

Can We Improve Outcomes in Patients With Previous Coronary Artery Bypass Surgery Admitted for Acute Coronary Syndrome

INTRODUCTION AND OBJECTIVES Prognosis and in-hospital management of patients with acute coronary syndrome (ACS) and a history of coronary artery bypass graft (CABG) surgery are still debated. The objective of this study was to characterize ACS patients with a CABG and to compare their in-hospital and postdischarge outcomes with those of patients without a CABG. METHODS This ongoing prospective observational study included 1,495 consecutive patients admitted for ACS to a coronary care unit and followed up for a mean of 19 months. There were two groups: group A (n=73), with CABGs; and group B (n=1,223), without CABGs. RESULTS Group A patients were more often male (86.3% versus 69.1%; P=.002), and more frequently had a history of diabetes, myocardial infarction and heart failure. Group B patients more frequently had ST-elevation myocardial infarction, and had a higher median ejection fraction (53% [interquartile range, 47%-60%] vs. 50% [42%-55%]; P< .01) and peak troponin-I concentration. There was no difference in the use of invasive techniques. Regarding medication, Group B patients were more likely to receive dual antiplatelet therapy at discharge. No significant difference was observed in in-hospital mortality (9.5% versus 5.9%; P=.2) or mortality at 1 month, 6 months or 1 year (9.8% versus 9.1%; log-rank test, P=.87) and the cumulative major adverse cardiac event rate was equally low in both groups. The presence of a CABG was associated with more readmissions for unstable angina (11.3% vs. 3.1%; P< .01). CONCLUSIONS In our ACS patients, the presence of a CABG had no significant influence on short- or medium-term outcomes, such as all-cause mortality and adverse cardiac events.

Impact of previous insulin therapy on the prognosis of diabetic patients with acute coronary syndromes

OBJECTIVE To determine whether previous insulin treatment independently influences subsequent outcomes in diabetic patients with ACS (acute coronary syndromes). SUBJECTS AND METHODS 375 diabetic patients with ACS, divided in 2 groups: Group A (n = 69)--previous insulin and Group B (n = 306)--without previous insulin. Predictors of 1-year mortality and major adverse cardiac events (MACE) were analyzed by Cox regression analysis. RESULTS Group A had more previous stroke (17.4% vs. 9.2%, p = 0.047) and peripheral artery disease (13.0% vs. 3.6%, p = 0.005). They had significantly higher admission glycemia and lower LDL cholesterol. There were no significant differences in the type of ACS, in 1-year mortality (18.2% vs. 10.4%, p = 0.103) or MACE (32.1% vs. 23.0%, p = 0.146) between groups. In multivariate analysis, insulin treatment was neither an independent predictor of 1-year mortality nor of MACE. CONCLUSION Despite the more advanced atherosclerotic disease, diabetics under insulin had similar outcomes to those without insulin. Insulin may protect diabetics from the expected poor adverse outcome of an advanced atherosclerotic disease.

Challenges in Vascular Repair by Endothelial Progenitor Cells in Diabetic Patients

Endothelial progenitor cells (EPCs) are a special type of stem cells, derived from bone marrow that can be mobilized to the peripheral circulation in response to many stimuli. EPCs play a crucial role in the vascular repair, as well as in neovascularization processes. Recent studies have shown that EPCs are impaired, both in number and function, in diabetic patients independently of other cardiovascular risk factors. Accelerated atherosclerosis is probably the most devastating among diabetes complications and endothelial dysfunction might be the beginning of the atherosclerosis. The impairment of EPCs seems to significantly contribute to atherogenesis and atherosclerotic disease progression in diabetes. Autologous EPCs therapy represents a novel treatment option for vascular complications requiring therapeutic revascularization and vascular repair. Diabetic patients represent a population that may benefit from cell-based therapy; however the dysfunction of their endogenous cells may limit the feasibility of this approach. In fact, EPCs isolated from these patients for autologous cell transplantation may retain their dysfunctional characteristics in vivo and as a consequence display a reduced capacity to improve therapeutic neovascularization. In the present review, we summarize the most relevant mechanisms of EPC dysfunction in diabetes.

A importância de um EGC normal em síndromes coronarianas agudas sem supradesnivelamento do segmento ST

FUNDAMENTO: El electrocardiograma (ECG) de ingreso tiene un gran impacto en el diagnostico y tratamiento de sindromes coronarios agudos (SCA) sin supradesnivel del segmento ST. OBJETIVO: Evaluar el impacto del ECG de ingreso en el pronostico del SCA sin supradesnivel de ST. METODOS: Poblacion: estudio prospectivo, continuo, observacional, de 802 pacientes con SCA sin supradesnivel de ST de un unico centro. Los pacientes se dividieron en 2 grupos: A (n=538) - ECG Anormal y B (n=264) - ECG Normal. ECG Normal era sinonimo de ritmo sinusal sin alteraciones isquemicas agudas. Se realizo un seguimiento clinico de un ano teniendo como objetivo todas las causas de mortalidad y la tasa de eventos cardiacos adversos mayores (MACE). RESULTADOS: Los pacientes del Grupo A eran mas viejos (68,7±11,7 vs 63,4±12,7 anos, p<0,001), presentaban clases Killip mas altas y picos mas altos de biomarcadores de necrosis miocardica. Ademas de ello, presentaban menor fraccion de eyeccion del ventriculo izquierdo (FEVI) (52,01±10,55 vs 55,34± 9,51%, p<0,001), tasa de filtrado glomerular, hemoglobina inicial, y niveles de colesterol total. Los pacientes del Grupo B fueron sometidos mas frecuentemente a estrategias invasivas (63,6 vs 46,5%, p<0,001) y tratados con aspirina, clopidogrel, betabloqueantes y estatinas. Estos tambien presentaban mas frecuentemente una anatomia coronaria normal (26,2 vs 18,0%, p=0,45). Se observo una tendencia a la mayor mortalidad hospitalaria en el grupo A (4,6 vs 1,9%, p=0,054). El analisis de Kaplan-Meyer mostro que la sobrevida de 1 mes y un ano (95,1 vs 89. 5%, p=0.012) era mas alta en el grupo B y el resultado se mantuvo significativo en un modelo de regresion de Cox (ECG normal HR 0,45 (0,21 - 0,97). No hubo diferencias con relacion a la tasa de MACE. CONCLUSION: En nuestra poblacion de pacientes son SCA sin supradesnivel de ST, un ECG normal fue un marcador inicial para un buen pronostico.BACKGROUND Admission ECG has a major impact on the diagnosis and management of non-ST elevation acute coronary syndromes (ACS). OBJECTIVE To assess the impact of the admission ECG on prognosis over non-ST ACS. POPULATION prospective, continuous, observational study of 802 non-ST ACS patients from a single center. METHODS Patients were divided in 2 groups: A (n=538) - Abnormal ECG and B (n=264) - Normal ECG. Normal ECG was synonymous of sinus rhythm and no acute ischemic changes. A one-year clinical follow up was performed targeting all causes of mortality and the MACE rate. RESULTS Group A patients were older (68.7+/-11.7 vs. 63.4+/-12.7Y, p<0.001), had higher Killip classes and peak myocardial necrosis biomarkers. Furthermore, they had lower left ventricular ejection fraction (LVEF) (52.01+/-10.55 vs. 55.34+/- 9.51%, p<0.001), glomerular filtration rate, initial hemoglobin, and total cholesterol levels. Group B patients were more frequently submitted to invasive strategy (63.6 vs. 46.5%, p<0.001) and treated with aspirin, clopidogrel, beta blockers and statins. They also more often presented normal coronary anatomy (26.2 vs. 18.0%, p=0.45). There was a trend to higher in-hospital mortality in group A (4.6 vs. 1.9%, p=0.054). Kaplan-Meyer analysis showed that at one month and one year (95.1 vs. 89.5%, p=0.012) survival was higher in group B and the result remained significant on a Cox regression model (normal ECG HR 0.45 (0.21 - 0.97). There were no differences regarding the MACE rate. CONCLUSION In our non-ST elevation ACS population, a normal ECG was an early marker for good prognosis.

Intrinsic Vascular Repair by Endothelial Progenitor Cells in Acute Coronary Syndromes: an Update Overview

Bone marrow-derived endothelial progenitor cells (EPCs) play a key role in the maintenance of endothelial homeostasis and endothelial repair at areas of vascular damage. The quantification of EPCs in peripheral blood by flow cytometry is a strategy to assess this reparative capacity. The number of circulating EPCs is inversely correlated with the number of cardiovascular risk factors and to the occurrence of cardiovascular events. Therefore, monitoring EPCs levels may provide an accurate assessment of susceptibility to cardiovascular injury, greatly improving risk stratification of patients with high cardiovascular risk, such as those with an acute myocardial infarction. However, there are many issues in the field of EPC identification and quantification that remain unsolved. In fact, there have been conflicting protocols used to the phenotypic identification of EPCs and there is still no consensual immunophenotypical profile that corresponds exactly to EPCs. In this paper we aim to give an overview on EPCs-mediated vascular repair with special focus on acute coronary syndromes and to discuss the different phenotypic profiles that have been used to identify and quantify circulating EPCs in several clinical studies. Finally, we will synthesize evidence on the prognostic role of EPCs in patients with high cardiovascular risk.

Ablação de taquicardia auricular em cardiopatia congénita operada

The authors describe the case of a 57-year-old woman with surgically treated superior vena cava sinus-venosus atrial septal defect who underwent an electrophysiology study with the CARTO ® 3 mapping system (Biosense Webster, J&J) due to recurrent episodes of tachycardia. The patient was found to be in narrow QRS-complex tachycardia, with a cycle length of 310 ms and concentric activation sequence in the coronary sinus (Figure 1A and 1B), suggesting atrial tachycardia (AT) originating from the right atrium (RA). High-density electroanatomical mapping of the RA was performed using the PentaRay catheter (Figure 2C). The AT activation map (Figure 2B) indicated microreentry and centrifugal activation mainly on the lateral RA wall (Figure 2B), coinciding with the border zone of the scar (Figure 2C) and reveals ≥75% of the tachycardia cycle on the PentaRay catheter (Figure 2A). Radio frequency was applied with the SmartTouch ablation catheter in the initial activation region, resulting in conversion to sinus rhythm (SR).

Redução da inflamação sistémica após terapêutica de ressincronização cardíaca: uma nova forma de resposta?

Chronic heart failure (CHF) is the final common pathway for various cardiac pathologies and, despite significant progress in its treatment in recent years, this complex clinical syndrome still has a poor prognosis. Cardiac resynchronization therapy (CRT) is a wellestablished option in the treatment of CHF that results in significant clinical improvements, ventricular reverse remodeling, and lower mortality in selected patients. However, based on current selection criteria, a significant proportion of patients with CHF do not respond positively to CRT. It is therefore important to identify new predictors that will improve the selection of potential responders to this therapy. Although the pathophysiology of CHF is still poorly understood, neurohormonal stimulation and immune activation have been shown to be involved in the development and progression of this systemic disease. There is growing evidence that levels of various pro-inflammatory cytokines are elevated in patients with CHF, and that this inflammatory