Conservative strategy for treatment of stable coronary artery disease

Patients with coronary artery disease vary widely in terms of prognosis, which is mainly dependent on ventricular function. In relation to the major outcomes of death and myocardial infarction, it is not clear in the literature if an invasive strategy of myocardial revascularization is superior to a conservative strategy of optimized medical therapy. Moreover, with the exception of patients with left main coronary disease, this similarity in prognosis also occurs in different subgroups of patients.

Juvenile hemochromatosis:HAMP mutation and severe iron overload treated with phlebotomies and deferasirox

Juvenile hemochromatosis(JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage,hypogonadotropic hypogonadism,cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation(g.47G>A),treated with phlebotomies and deferasirox. She presented symptoms such as weakness,skin hyperpigmentation,joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin(SF): 5696 ng/mL,transferrin saturation(TS): 85%]. After sessions of phlebotomies(450 mL every 15 d),the patient presented partial symptomatic improvements and biochemical parameters(SF: 1000 ng/mL,Hb: 11 g/dL). One year later,deferasirox(15 mg/kg per day) was introduced to the treatment,and the patient showed total symptomatic improvement,with significant clearing of the skin,SF: 169 ng/mL,and TS: 50%. Furthermore,after the combined deferasirox-phlebotomy therapy,magnetic resonance imaging measurements revealed normalized level for liver iron(30 μmol/g; reference value < 36 μmol/g). In conclusion,combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms.

Imaging response predictors following drug eluting beads chemoembolization in the neoadjuvant liver transplant treatment of hepatocellular carcinoma

BACKGROUND Drug-eluting bead transarterial chemoembolization(DEB-TACE)is an endovascular treatment to release chemotherapeutic agents within a target lesion,minimizing systemic exposure and adverse effects to chemotherapeutics.Therefore,identifying which patient characteristics may predict imaging response to DEB-TACE can improve treatment results while selecting the best candidates.Predictors of the response after DEB-TACE still have not been fully elucidated.This is the first prospective study performed with standardized DEBTACE technique that aim to identify predictors of radiological response,assessing patients clinical and laboratory characteristics,diagnostic imaging and intraprocedure data of the hepatocellular carcinoma treated in the neoadjuvant context for liver transplantation.AIM To identify pre-and intraoperative clinical and imaging predictors of the radiological response of drug-eluting bead transarterial chemoembolization(DEB-TACE)for the neoadjuvant treatment of hepatocellular carcinoma(HCC).METHODS This is prospective,cohort study,performed in a single transplant center,from 2011 to 2014.Consecutive patients with HCC considered for liver transplant who underwent DEB-TACE in the first session for downstaging or bridging purposes were recruited.Pre and post-chemoembolization imaging studies were performed by computed tomography or magnetic resonance.The radiological response of each individual HCC was evaluated by objective response using mRECIST and the percentage of necrosis.RESULTS Two hundred patients with 380 HCCs were examined.Analysis of the objective response(nodule-based analysis)demonstrated that HCC with pseudocapsules had a 2.01 times greater chance of being responders than those without pseudocapsules(P=0.01),and the addition of every 1mg of chemoembolic agent increased the chance of therapeutic response in 4%(P<0.001).Analysis of the percentage of necrosis through multiple linear regression revealed that the addition of each 1mg of the chemoembolic agent caused an average increase of 0.65%(P<0.001)in necrosis in the treated lesion,whereas the hepatocellular carcinoma with pseudocapsules presented 18.27%(P<0.001)increased necrosis compared to those without pseudocapsules.CONCLUSION The presence of a pseudocapsule and the addition of the amount of chemoembolic agent increases the chance of an objective response in hepatocellular carcinoma and increases the percentage of tumor necrosis following drug-eluting bead chemoembolization in the neoadjuvant treatment,prior to liver transplantation.

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Chagas disease cardiomyopathy(CCC), the main consequence of Trypanosoma cruzi(T.cruzi) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon(IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.

A Risk-Adjusted Retrospective Data Analysis between Younger and Elderly Patients with Acute Coronary Syndromes—Long-Term Prognosis

Purpose: To compare the demographic data and outcomes of younger versus elderly patients with acute coronary syndromes. Methods: This was a retrospective data bank analysis study with 966 patients (268 in the younger group (less than 55 years) and 698 in the elderly group (more than 55 years)). Data were obtained about clinical characteristics, angiography, and medication used at hospital and coronary definitive treatment. The primary endpoint was all cause of in-hospital death and combined events. Comparison between groups was made by Anova and Q-square. Multivariative analysis was determined by logistic regression and was considered significative when p < 0.05. Long-term mortality and combined events were studied using Kaplan- Meyer curves with median follow-up of 11.21 months. Results: The median age in the younger group was 48 years versus 69 years in the elderly group. In the younger group 26% was ST-myocardial infarction versus 18% in the elderly group. About 7% of younger patients were submitted to coronary bypass surgery and 42% to percutaneous coronary angioplasty versus 12% and 25% in elderly group, respectively. Significant difference was observed between the younger versus elderly groups in deaths (1.5% × 7.5%, p = 0.004), combined events (14.9% × 26.3%, p = 0.02) and killip III/IV (3.7% × 8.3%, p = 0.04). Long-term mortality was 3.7% × 10.2%, p = 0.01). Conclusions: In patients with acute coronary syndromes age was an important predictor factor of mortality and complications. Significative differences in outcomes were observed between the two groups in-hospital and long-term follow-up.

2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma

AIM:To assess the prognostic value and risk classification improvement of metabolic staging(MS)with Initial2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography(FDG-PET)in initial staging of Hodgkin’s Lymphoma(HL)patients to predict 5 years overall survival(5y-OS)and event free survival(EFS).METHODS:A total of 275 patients were included in this retrospective study,155 patients were staged with conventional anatomical staging(AS),and 120 also submitted to MS(FDG-PET).Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS.Risk-adjusted models incorporated clinical risk factors,computed tomography and FDG-PET staging.RESULTS:During the follow up of 267 evaluated patients,220(122 AS and 98 MS)achieved complete remission after first-line therapy(median follow-up:70±29 mo),treatment failure occurred in 79 patients and 34 died.The 5y-EFS for early vs advanced disease in AS patients was 79.3%and 66.7%,and 85.6%and53.6%in MS patients,respectively(P<0.01).The5y-OS for early and advanced disease with AS was91.3%and 81.5%,and 97.5%and 80.7%for patients staged with MS,respectively.Cox proportional hazards analysis demonstrated that FDG-PET added signifcant prognostic information and improved risk prediction(P=0.02).CONCLUSION:Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL,with impact in 5y-EFS and OS.

Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics

Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications.Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies.Methods:We analyzed a prospective cohort of 52 pediatric patients(age 3 to 35 months)looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery,defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography.This corresponds to a mean pulmonary arterial pressure of>20 mmHg.Clinical,echocardiographic and hemodynamic parameters were investigated.Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters.Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio(PAP/SAP)obtained per patient during the first 6 h of postoperative care.Results:Among the factors that were investigated as possible predictors,perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis(p<0.030).Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass(r=0.70,p<0.001),and it was higher in subjects with Down syndrome than in nonsyndromic individuals(p=0.003).Early postoperative PAP/SAP was the only predictor selected using multivariate analysis.It was characterized as an independent predictor after adjustments for possible confounders.An early postoperative PAP/SAP of>0.35 was 76%sensitive and 74%specific at predicting a systolic pulmonary arterial pressure of>30 mmHg 6 months after surgery(hazard ratio with 95%CI 8.972[2.428–33.158],p=0.002).Conclusion:The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome,and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.

Oral PTCTS (Particulated Transialidase) Removes Serum Microparticles and Decreases Inflammation in Atherosclerotic Plaques of Rabbits

Background: Previous studies showed that atherosclerotic plaque vulnerability was related with microparticles (MPs)-vesicles larger than 100 nm, which released MMP9 collagenase. In our previous study, intramuscular injection of a new drug (PTCTS) normalized oxidized LDL serum levels and reduced rabbit atherosclerosis. Now, we studied administration of oral PTCTS in order to clarify anti-atherosclerotic mechanism of action, analyzing if the treatment removed MPs containing ox-LDL and Mycoplasma pneumoniae antigens and improved the immune response. Methods: We compared two groups of rabbits. Control group (CG, n = 6)—1% cholesterol enriched diet for 12 weeks;Treated group (TG, n = 8)—1% cholesterol enriched diet for 12 weeks with administration of PTCTS (400 μl/day) during the last 6 weeks of diet. The animals had their blood collected, in three different phases of the protocol before being fed with hypercholesterolemic diet, before being treated with water or PTCTS and at the moment of sacrifice. The serum was submitted to immunofluorescence technique to evaluate the quantity of microparticles marked with antibodies against Mycoplasma pneumoniae and ox-LDL. A fragment of aorta was submitted to immunohistochemical detection of antigens from MMP9, ox-LDL, NF-κB and IL-1β. Results: PTCTS showed significant reduction in MMP-9 (P = 0.001) and a tendency of reducing IL-1β (P = 0.09) in the aortic plaques compared with CG. In the serum, PTCTS was able to remove microparticles containing antigen of ox-LDL (P = 0.004) and Mycoplasma pneumoniae (P β and mycoplasma, as well as a better stabilization of the atheromatous plaque by reducing levels of MMP-9, avoiding plaque rupture, without causing mortality or toxicity.

Safety and Efficacy of PTCTS Cosmetic Gel: Study on Human Radiodermatitis Lesions

Radiodermatitis is a constant complication after radiotherapy with no efficient drug for prevention and treatment. Its physiopathology is complex, possibly related to injury of epidermis and endothelial cells from the basal layer by radiolysis, overproduction of free radicals, pro-inflammatory cytokines, and inflammation. PTCTS gel is an after sun cosmetic gel composed by anti-oxidative plant extract rich in natural nanoparticles and thermal water (Complex A) and recombinant protein of Trypanosoma cruzi transialidase (Complex B), with high anti-oxidative and anti-apoptotic effects, presenting anti-aging and healing cutaneous properties. Objective: To study the safety and efficacy of PTCTS gel for topic use in volunteer subjects with healthy skin, and in patients with radiodermatitis, in different concentrations of Complexes A and B. Material and Methods: The project was approved by the Ethical Committee of Arnaldo Vieira de Carvalho Institute, Sao Paulo, Brazil. The individuals were submitted to laboratorial toxicity study through tests for liver and kidney function, levels of blood glucose and blood count before and after 7 days of PTCTS application. We studied two groups: GI-22 volunteers with healthy skin, presenting articular or skeletal muscle pain and GII-38 patients in radiotherapy for breast or head and neck cancer, with radiodermatitis grade 2 or 3. The patients were evaluated before and after 1.0 ml/cm2 PTCTS gel application, twice a day. We tested Complex B in four different concentrations, and Complex A concentrations varied inversely. Results: No irritation signs were observed in GI nor GII group, 64% of GI had important decrease in the intensity of the muscular or articular pain, and 99% of GII showed regression of radiodermatitis, all exhibiting relief of pain. No patient presented hematologic, renal or hepatic toxicity. Conclusion: PTCTS cosmetic gel is a safe option for radiodermatitis treatment, with no side effects or laboratorial toxicity in different concentrations. This product presented excellent clinical results even if used diluted 4 times more than the original product and may be a good option for treatment of radiodermatitis. Further studies may show if it is also indicated in the prevention of the lesion, and if it is better than products containing corticoids.

平面心肌灌注成像评价急性胸痛患者的价值

Background: Rest single-photon emission computed tomographic(SPECT) perfusion imaging identifies acute myocardial ischemia in patients with chest pain in the emergency department; however, the costs are high and radioisotopic services are usually not available 24 h a day. Planar imaging through a portable gamma camera may be useful in this setting. However, planar imaging might be associated with less predictive values in comparison with a gated SPECT imaging. We sought to evaluate rest planar myocardial perfusion imaging for evaluation and triage of patients with suspected acute cardiac ischemia. Methods: Patients within 6 h of chest pain onset and nondiagnostic electrocardiograms(ECGs) underwent planar myocardial perfusion imaging. Studies showing perfusion defects were considered suggestive of acute coronary syndromes. The results of planar scintigraphy were compared with the clinical diagnosis and outcomes. All patients were followed up and monitored for the occurrence of major cardiac events 120 days after hospital discharge. Results: 71 patients underwent scintigraphy. Twenty-one(30%) patients had acute coronary syndromes, 15(21%) had major cardiac events(8 had myocardial infarction and 7 underwent myocardial revascularization). Planar scintigraphy demonstrated perfusion defects in 21 patients, 16 (76%) patients with acute coronary syndromes, 12(80%) patients who had major cardiac events and in 7(88%) patients with myocardial infarction. The negative predictive value of planar scintigraphy was 90%for diagnosis of acute coronary syndromes and 94%for detecting major cardiac events. Conclusion: Early planar myocardial perfusion imaging allowed rapid and accurate risk stratification of emergency departments patients with possible myocardial ischemia and nondiagnostic ECGs.

健康巴西人群的高敏感性C-反应蛋白浓度

Background: The use of serum high-sensitivity C-reactive protein(hs-CRP) for cardiovascular risk profiling requires knowledge of the distribution in different populations. We studied serum hs-CRP in a healthy Brazilian population, with no evidence of heart disease, relative to gender and smoking status as well as other clinical and laboratory variables. Methods: 684 healthy Brazilian individuals, aged 14-74 years(mean 40-.6 years), 295 men(43.1%) and 389 women(56.9%), were enrolled between July 1998 and July 2001. The relationship between the log-transformed hs-CRP, stratified by gender and smoking status(non-smokers, smokers), and clinical and laboratory variables were analyzed using the Spearman correlation coefficient and multiple linear regression. Results: In a multiple linear regression model age(β=1.0069, p=0.03), body mass index(BMI) (β=1.0093, p< 0.01), total cholesterol/HDL cholesterol ratio(TC/HDL-C)(β=1.1015, p< 0.01) and heart rate(β=1.0139, p< 0.01) were independently correlated with hs-CRP. Stratification according to gender and smoking was able to disclose different interactions between these variables and hs-CRP. Variables significantly correlated in each stratum were as follows: in smoker men, age(β=1.0236, p=0.04) and TC/HDL-C (β=1.2065, p< 0.01); in non-smoker men, BMI(β=1.0786, p< 0.01) and TC/HDL-C(β=1.1397, p=0.01); in smoker women, BMI(β=1.1006, p=0.03); and in non-smoker women, BMI (β=1.0873, p< 0.01), TC/HDL-C(β=1.1405, p=0.01) and heart rate(β=1.0165, p=0.02). Conclusions: The clinical and laboratory variables studied influenced the concentration of hs-CRP according to gender and smoking. In assessing the risk of cardiovascular events in relation to serum hs-CRP level, stratification by gender and smoking status is indicated.

血管紧张素转换酶基因缺失多态性对心力衰竭患者症状发生和生存率的调节

Background: Angiotensin-converting enzyme is involved in the pathophysiology of heart failure. We hypothesized that clinical characteristics as well as survival rate in patients with heart failure of different etiologies may be modulated by functional variants DD, ID and II of the angiotensin-converting enzyme gene. Methods: We studied 333 patients with heart failure, aged 43.3±10.5 years, 262(78.7%) men and 71(21.3%) women. Heart failure was ascribed to idiopathic dilated cardiomyopathy in 125 patients. Heart failure was caused by ischemic heart disease in 63 patients, Chagas’disease in 58, hypertensive heart disease in 41, alcoholic cardiomyopathy in 24, and was due to other etiologies in 22 patients. Statistical analysis was performed with the χ2 test, Student’s t-test, analysis of variance, Kaplan-Meier and Cox proportional hazards methods. Results: The DD genotype was associated with increased systolic left ventricular diameter(p=0.031). Earlier onset of symptoms was observed in patients with alcoholic cardiomyopathy and DD genotype(p=0.033, codominant D) and in patients with hypertensive cardiomyopathy and DD genotype(p=0.048, codominant D; p=0.024, recessive D). Mortality was higher in patients older than 50 years with DD genotype(p=0.007, codominant D; p=0.002, recessive D). Variables independently associated with higher mortality in patients older than 50 years were age, diabetes mellitus, Chagas’disease etiology and DD genotype. Conclusions: These results add evidence for an association of the DD genotype of the angiotensin-converting enzyme gene with earlier onset of symptoms and decreased survival rate of selected patients with heart failure.

依那普利对无症状或症状轻微的因二尖瓣脱垂或风心病继发二尖瓣反流患者的左心室直径和运动耐量的影响

The effects of 12 months of therapy were evaluated in 47 mildly symptomatic patients with moderate to severe mitral valve regurgitation; 26 patients received enalapril and 21 received a placebo. Enalapril was associated with a significant reduction in left ventricular diameter and mitral regurgitation volume, with no evidence of change in systolic function indexes. However, enalapril did not hinder progressive aerobic impairment to effort.

不稳定型心绞痛和PTCA术后患者血小板和白细胞的黏附和激活

Background: Unstable atherosclerotic plaques activate blood cells which may adhere to the coronary endothelium causing vessel occlusion. However, it is unknown if different clinical syndromes associated with plaque rupture induce similar blood cell activation and adhesion to the endothelium. Methods: We studied changes in adhesion molecule expression of platelets(GPIIb/IIIa), neutrophils -CD18, CD11b and L-selectin -and monocytes(CD14) after interaction with active lesions of patients with stable angina subjected to PTCA and patients with unstable angina(UA). Generation of superoxide(SO) radicals from PMNs and PMN sequestration in the coronary circulation were also assessed. Blood samples were collected from the aorta(Ao) and coronary sinus(CS) before and 15 min after PTCA(n=13) and within the first 48 h of UA(n=12). Results: PTCA induced a marked up-regulation of CD18, CD11b, CD14 and GPIIb/IIIa with L-selectin shedding and reduced SO formation, whereas only minor L-selectin down-regulation and decreased SO production indicated activation in UA. However, a significant decrease in neutrophil count in the CS compared to the Ao was only observed in UA. Conclusions: The magnitude of cellular activation depends on the underlying clinical setting and just partially contributes to cell adhesion to the endothelium which might be modulated by different extent of vascular occlusion and shear forces.

肌细胞直径和胶原面积分数与特发性扩张型心肌病门诊患者的存活时间无关:一项基于右室心肌内膜活检的研究

来自心肌内膜活检分析的形态数据可能有助于评价扩张型心肌病患者的预后。作者检查了35例特发性扩张型心肌病门诊患者右室心肌内膜活检标本中的肌细胞直径、其变异系数以及胶原面积分数。研究中所有的组织学参数均与患者的存活时间无关（极差2～5588d，中位时间706d）。不应使用右室心肌内膜活检来预测特发性扩张型心肌病患者的进展或致死性结局。

Pathogenesis of Chagas disease cardiomyopathy

Chagas disease, or American trypanosomiasis, is a parasitic infection caused by the flagellate protozoanTrypanosoma cruzi. Chagas disease is mainly affecting rural populations in Mexico and Central and South America. The World Health Organization estimates that 300 000 new cases of Chagas disease occur every year and approximately 20 000 deaths are attributable to Chagas. However, this organisation classified Chagas disease as a neglected tropical disease. The economic burden of this disease is significant. In many Latin American countries, the direct and indirect costs, including the cost of health care in dollars and loss of productivity, attributable to Chagas disease ranges from $40 million to in excess of $800 million per nation per annum. So, it remains a contemporary public health concern. In chronic phase, mortality is primarily due to the rhythm disturbances and congestive heart failure that result from the chronic inflammatory cardiomyopathy(CCC) due to the persistence presence of parasites in the heart tissue. Mechanisms underlying differential progression to CCC are still incompletely understood. In the last decades immunological proteomic genetic approaches lead to significant results which help to disperse the veil covering the knowledge of the pathogenic process. Here, we reported these significant progresses.