Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease

Background UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function. Methods The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan–Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model. Results There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients. Conclusions These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.

Clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome

AIM: to assess the clinical evolution of patients hospitalized due to the first episode of Acute Coronary Syndrome (ACS) according to its clinical manifestation. METHODS: data were collected from 234 patients, hospitalized between May 2006 and July 2009 due to the first episode of an ACS, by consulting their medical records. RESULTS: 234 patients were hospitalized, 140 (59.8%) due to Acute Myocardial Infarction (AMI). In the group with AMI, 19.3% presented complications, against 12.8% in the group with Unstable Angina (UA) (p=0.19). Angioplasty levels were higher among patients with AMI than with UA (p=0.02) and coronary artery bypass graft surgery was more frequent among UA patients (p=0.03). The majority (227; 97%) survived after the coronary event. Among the seven patients who died during the hospitalization, four had AMI (2.9%) and three UA (3.2%). CONCLUSIONS: A larger number of complications were found among infarction victims and the accomplishment of coronary artery bypass graft surgery differed between the groups.

Assessment of cardiovascular risk of patients with arterial hypertension of a public health unit

OBJECTIVE: To assess the cardiovascular risk, using the Framingham risk score, in a sample of hypertensive individuals coming from a public primary care unit. METHODS: The caseload comprised hypertensive individuals according to criteria established by the JNC VII, 2003, of 2003, among 1601 patients followed up in 1999, at the Cardiology and Arterial Hypertension Outpatients Clinic of the Teaching Primary Care Unit, at the Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. The patients were selected by draw, aged over 20 years, both genders, excluding pregnant women. It was a descriptive, cross-sectional, observational study. The Framingham risk score was used to stratify cardiovascular risk of developing coronary artery disease (death or non-fatal acute myocardial infarction). RESULTS: Age range of 27-79 years ( = 63.2 ± 9.58). Out of 382 individuals studied, 270 (70.7%) were female and 139 (36.4%) were characterized as high cardiovascular risk for presenting diabetes mellitus, atherosclerosis documented by event or procedure. Out of 243 stratified patients, 127 (52.3%) had HDL-C < 50 mg/dL; 210 (86.4%) had systolic blood pressure > 120 mmHg; 46 (18.9%) were smokers; 33 (13.6%) had a high cardiovascular risk. Those added to 139 enrolled directly as high cardiovascular risk, totaled up 172 (45%); 77 (20.2%) of medium cardiovascular risk and 133 (34.8%) of low risk. The highest percentage of high cardiovascular risk individuals was aged over 70 years; those of medium risk were aged over 60 years; and the low risk patients were aged 50 to 69 years. CONCLUSION: The significant number of high and medium cardiovascular risk individuals indicates the need to closely follow them up.

Pentraxin 3 accelerates lung injury in high tidal volume ventilation in mice

Mechanical ventilation is the major cause of iatrogenic lung damage in intensive care units. Although inflammation is known to be involved in ventilator-induced lung injury (VILI), several aspects of this process are still unknown. Pentraxin 3 (PTX3) is an acute phase protein with important regulatory functions in inflammation which has been found elevated in patients with acute respiratory distress syndrome. This study aimed at investigating the direct effect of PTX3 production in the pathogenesis of VILI. Genetically modified mice deficient and that over express murine Ptx3 gene were subjected to high tidal volume ventilation (V-T = 45 mL/kg, PEEPzero). Morphological changes and time required for 50% increase in respiratory system elastance were evaluated. Gene expression profile in the lungs was also investigated in earlier times in Ptx3-overexpressing mice. Ptx3 knockout and wild-type mice developed same lung injury degree in similar times (156 +/- 42 min and 148 +/- 41 min, respectively: p = 0.8173). However, Ptx3 overexpression led to a faster development of VILI in Ptx3-overexpressing mice (77 +/- 29 min vs 118 +/- 41 min, p = 0.0225) which also displayed a faster kinetics of Il1b expression and elevated Ptx3, Cxcl1 and Ccl2 transcripts levels in comparison with wild-type mice assessed by quantitative real-time polymerase chain reaction. Ptx3 deficiency did not impacted the time for VILI induced by high tidal volume ventilation but Ptx3-overexpression increased inflammatory response and reflected in a faster VILI development. (C) 2012 Elsevier Ltd. All rights reserved.

Left ventricular thrombus attenuation characterization in cardiac computed tomography angiography

BACKGROUND: Because of their similar visual appearance, differentiation of left ventricular thrombotic material and myocardial wall can be difficult in contrast-enhanced coronary computed tomography (CT) angiography. OBJECTIVE: We identified typical thrombi attenuation of left ventricular thrombi with the use of CT measurement. METHODS: Over a time period of 6 years; we retrospectively identified 31 patients who showed a left ventricular thrombus in CT angiography datasets. Patients underwent routine contrast cardiac CT to investigate coronary artery disease. CT attenuation of each thrombus was assessed in the 4-chamber view. CT densities were also determined in the ascending aorta, left ventricle, and myocardial wall both in the mid-septal and mid-lateral segments. The mean CT attenuation of thrombi and the difference between attenuation in thrombi, left ventricular cavity, and myocardial wall were determined. The ratio of attenuation values in thrombus versus aorta and myocardium versus aorta were also determined. RESULTS: Mean (+/- SD) CT attenuation of all left ventricular thrombi in 31 patients was 43.2 +/- 15.3 HU (range, 25-80 HU). Mean CT densities of septal and lateral myocardial wall were 102.9 +/- 23.1 HU (range, 63-155 HU) and 99.3 +/- 28.7 HU (range, 72-191 HU), respectively, and were thus significantly higher than the CT attenuation of thrombi (P < 0.001). A threshold of 65 HU yielded a sensitivity, specificity, and positive and negative predictive values of 94%, 97%, 94%, and 97%, respectively, to differentiate thrombus from the myocardial wall. The mean ratio between CT attenuation of thrombus and CT attenuation within the ascending aorta was 0.11 +/- 0.05 (range, 0.04-0.23), which was significantly lower compared with the mean ratio between CT attenuation of the myocardial wall and the CT attenuation within the ascending aorta. CONCLUSION: CT attenuation within left ventricular thrombi was significantly lower than myocardial attenuation in CT angiography datasets. Assessment of CT attenuation may contribute to the differentiation of thrombi. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved.

Cancer-related deaths among different treatment options in chronic coronary artery disease: results of a 6-year follow-up of the MASS II study

Introduction The primary end points of randomized clinical trials evaluating the outcome of therapeutic strategies for coronary artery disease (CAD) have included nonfatal acute myocardial infarction, the need for further revascularization, and overall mortality. Noncardiac causes of death may distort the interpretation of the long-term effects of coronary revascularization. Materials and methods This post-hoc analysis of the second Medicine, Angioplasty, or Surgery Study evaluates the cause of mortality of patients with multivessel CAD undergoing medical treatment, percutaneous coronary intervention, or surgical myocardial revascularization [coronary artery bypass graft surgery (CABG)] after a 6-year follow-up. Mortality was classified as cardiac and noncardiac death, and the causes of noncardiac death were reported. Results Patients were randomized into CABG and non-CABG groups (percutaneous coronary intervention plus medical treatment). No statistical differences were observed in overall mortality (P = 0.824). A significant difference in the distribution of causes of mortality was observed among the CABG and non-CABG groups (P = 0.003). In the CABG group, of the 203 randomized patients, the overall number of deaths was 34. Sixteen patients (47.1%) died of cardiac causes and 18 patients (52.9%) died of noncardiac causes. Of these, seven deaths (20.6%) were due to neoplasia. In the non-CABG group, comprising 408 patients, the overall number of deaths was 69. Fifty-three patients (77%) died of cardiac causes and 16 patients (23%) died of noncardiac causes. Only five deaths (7.2%) were due to neoplasia. Conclusion Different treatment options for multivessel coronary artery disease have similar overall mortality: CABG patients had the lowest incidence of cardiac death, but the highest incidence of noncardiac causes of death, and specifically a higher tendency toward cancer-related deaths. Coron Artery Dis 23:79-84 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Association between particulate matter air pollution and monthly inhalation and nebulization procedures in Ribeirao Preto, Sao Paulo State, Brazil

The study was designed to investigate the impact of air pollution on monthly inhalation/nebulization procedures in Ribeirao Preto, Sao Paulo State, Brazil, from 2004 to 2010. To assess the relationship between the procedures and particulate matter (PM10) a Bayesian Poisson regression model was used, including a random factor that captured extra-Poisson variability between counts. Particulate matter was associated with the monthly number of inhalation/nebulization procedures, but the inclusion of covariates (temperature, precipitation, and season of the year) suggests a possible confounding effect. Although other studies have linked particulate matter to an increasing number of visits due to respiratory morbidity, the results of this study suggest that such associations should be interpreted with caution.

Molecular mapping of the regenerative niche in a murine model of myocardial infarction

Adult stem cells are distributed through the whole organism, and present a great potential for the therapy of different types of disease. For the design of efficient therapeutic strategies, it is important to have a more detailed understanding of their basic biological characteristics, as well as of the signals produced by damaged tissues and to which they respond. Myocardial infarction (MI), a disease caused by a lack of blood flow supply in the heart, represents the most common cause of morbidity and mortality in the Western world. Stem cell therapy arises as a promising alternative to conventional treatments, which are often ineffective in preventing loss of cardiomyocytes and fibrosis. Cell therapy protocols must take into account the molecular events that occur in the regenerative niche of MI. In the present study, we investigated the expression profile of ten genes coding for chemokines or cytokines in a murine model of MI, aiming at the characterization of the regenerative niche. MI was induced in adult C57BL/6 mice and heart samples were collected after 24 h and 30 days, as well as from control animals, for quantitative RT-PCR. Expression of the chemokine genes CCL2, CCL3, CCL4, CCL7, CXCL2 and CXCL10 was significantly increased 24 h after infarction, returning to baseline levels on day 30. Expression of the CCL8 gene significantly increased only on day 30, whereas gene expression of CXCL12 and CX3CL1 were not significantly increased in either ischemic period. Finally, expression of the IL-6 gene increased 24 h after infarction and was maintained at a significantly higher level than control samples 30 days later. These results contribute to the better knowledge of the regenerative niche in MI, allowing a more efficient selection or genetic manipulation of cells in therapeutic protocols.

Strategies for Multivessel Revascularization in Patients with Diabetes

BACKGROUND In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease. METHODS In this randomized trial, we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure, and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients' mean age was 63.1 +/- 9.1 years, 29% were women, and 83% had three-vessel disease. The primary outcome occurred more frequently in the PCI group (P=0.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=0.03). CONCLUSIONS For patients with diabetes and advanced coronary artery disease, CABG was superior to PCI in that it significantly reduced rates of death and myocardial infarction, with a higher rate of stroke. (Funded by the National Heart, Lung, and Blood Institute and others; FREEDOM ClinicalTrials.gov number, NCT00086450.)

Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

Abstract Background: Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design: We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion: Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).

Cirurgia de revascularização miocárdica na fase aguda do infarto: análise dos fatores preditores de mortalidade intra-hospitalar

OBJETIVO: A cirurgia de revascularização miocárdica (CRM) na fase aguda do infarto do miocárdio (IAM) está associada a aumento do risco operatório. O objetivo do estudo foi determinar fatores preditores de mortalidade intra-hospitalar nos pacientes submetidos a CRM no IAM. MÉTODOS: Durante três anos, todos os pacientes submetidos a CRM no IAM foram analisados retrospectivamente, utilizando o banco de dados institucional. Sessenta variáveis por paciente foram avaliadas: 49 variáveis pré-operatórias provenientes dos escores 2000 Bernstein-Parsonnet e EuroSCORE; 4 variáveis pré-operatórias não consideradas por esses escores (tempo entre o IAM e a CRM, valor máximo de CKMB, valor máximo de troponina e supradesnivelamento do segmento ST) e 7 variáveis intraoperatórias [uso de circulação extracorpórea (CEC), tempo de CEC, tipo de cardioplegia, endarterectomia, número de enxertos, uso da artéria torácica interna e revascularização completa]. Análise univariada e multivariada para o desfecho mortalidade intra-hospitalar foram realizadas. RESULTADOS: O tempo médio entre o IAM e a CRM foi de 3,8 ± 3 dias. A mortalidade global foi 19%. Na análise multivariada: idade > 65 anos [OR 16,5 (IC 1,8-152), P=0,013]~ CEC >108 minutos [OR 40 (IC 2,7-578), P=0,007], creatinina > 2 mg/dl [OR 35,5 (IC 1,7-740), P=0,021] e pressão pulmonar sistólica > 60 mmHg [OR 31(IC 1,6-591), P=0,022] foram preditores de mortalidade intra-hospitalar. CONCLUSÃO: Variáveis pré-operatórias clássicas como idade > 65 anos, creatinina > 2 mg/dl e pressão pulmonar sistólica > 60 mmHg foram preditoras de mortalidade intra-hospitalar nos pacientes operados de revascularização miocárdica na fase aguda do infarto.

Age influences outcomes in 70-year or older patients undergoing isolated coronary artery bypass graft surgery

Objective: To analyze the results of isolated on-pump coronary artery bypass graft surgery (CABG) in patients >= 70 years old in comparison to patients <70 years old. Methods: Patients undergoing isolated CABG were selected for the study. The patients were assigned into two groups: G1 (age >= 70 years old) and G2 (age <70 years old). The endpoints were in-hospital mortality, acute myocardial infarction (AMI), stroke, re-exploration for bleeding, intraaortic balloon pump for circulatory shock, respiratory complications, acute renal failure, mediastinitis, sepsis, atrial fibrillation, and complete atrioventricular block (CAVB). Results: A total of 1,033 were included in the study: G1 comprised 257 (24.8%) patients G2 776 (75.2%). Patients in G1 were more likely to have in-hospital mortality than in G2 (8.9% vs. 3.6%, respectively; P=0.001), while the incidence of AMI was similar (5.8% vs. 5.5%; P=0.87) in G2. More patients in G1 had re-exploration for bleeding (12.1% vs. 6.1%; P=0.003). Compared to G2, G1 had more incidences of respiratory complications (21.4% vs. 9.1%; P<0.001), mediastinitis (5.1% vs. 1.9%; P=0.013), stroke (3.9% vs. 1.3%; P=0.016), acute renal failure (7.8% vs. 1.3%; P<0.001), sepsis (3.9% vs. 1.9%; P=0.003), atrial fibrillation (15.6% vs. 9.8%; P=0.016), and CAVB (3.5% vs. 1.2%; P=0.023). There was no significant difference in the use of the intraaortic balloon pump. In the forward stepwise multivariate logistic regression analysis, age >= 70 years was an independent predictive factor for higher in-hospital mortality (P=0.004), re-exploration for bleeding (P=0.002), sepsis (P=0.002), respiratory complications (P<0.001), mediastinitis (P=0.016), stroke (P=0.029), acute renal failure (P<0.001), atrial fibrillation (P=0.021), and CAVB (P=0.031). Conclusion: This study suggests that patients of age >= 70 years were at increased risk of death and other complications in the CABG's postoperative period in comparison to younger patients.

Infarto agudo do miocárdio após operações não cardíacas

Em todo o mundo, são realizadas mais de 230 milhões de operações por ano e as complicações cardíacas são as causas mais comuns de morbidade e mortalidade pós-operatórias. Com o aumento da expectativa de vida da população mundial, um número crescente de pacientes com múltiplas comorbidades tem sido submetido a operações não cardíacas. Em consequência, é esperado um aumento de complicações cardiovasculares associadas a tais procedimentos e o infarto agudo do miocárdio (IAM) perioperatório poderá se tornar um problema frequente. No Brasil, o número de operações não cardíacas também está aumentando, sendo realizadas aproximadamente três milhões de cirurgias por ano. Apesar dos avanços nas técnicas cirúrgicas e anestésicas, a mortalidade e o custo relacionados a estes procedimentos também estão aumentando, sendo fundamental o desenvolvimento de estratégias para a redução da mortalidade. A ocorrência de um IAM perioperatório prolonga a necessidade de terapia intensiva, a estadia hospitalar, aumenta o custo da internação e diminui a sobrevida a longo prazo. Esta revisão aborda a fisiopatologia, a incidência, o diagnóstico e o tratamento do IAM perioperatório, baseado nas evidências atuais.

Segurança da intervenção fisioterápica precoce após o infarto agudo do miocárdio

INTRODUÇÃO: A fisioterapia na fase I da reabilitação cardiovascular (FTCV) pode ser iniciada de 12 a 24 horas após o infarto agudo do miocárdio (IAM), no entanto, é comum o repouso prolongado no leito em razão do receio de instabilização do paciente. OBJETIVOS: Avaliar as respostas autonômicas e hemodinâmicas de pacientes pós-IAM submetidos ao primeiro dia de protocolo de FTCV fase I, bem como sua segurança. MATERIAIS E MÉTODOS: Foram estudados 51 pacientes com primeiro IAM não complicado, 55 ± 11 anos, 76% homens. Foram submetidos ao primeiro dia do protocolo de FTCV fase I, em média 24 horas pós-IAM. A frequência cardíaca (FC) instantânea e os intervalos R-R do ECG foram captados pelo monitor de FC (Polar®S810i) e a pressão arterial (PA) aferida pelo método auscultatório. A variabilidade da FC foi analisada nos domínios do tempo (RMSSD e RMSM dos iR-R em ms) e da frequência. A densidade espectral de potência foi expressa em unidades absolutas (ms²/Hz) e normalizada (un) para as bandas de baixa (BF) e alta frequência (AF) e pela razão BF/AF. RESULTADOS: O índice RMSSD, a AF e a AFun apresentaram redução na execução dos exercícios em relação ao repouso pré e pós-exercício (p < 0,05), a BFun e a razão BF/AF aumentaram (p < 0,05). A FC e a PA sistólica apresentaram aumento durante a execução dos exercícios em relação ao repouso (p < 0,05). Não foi observado qualquer sinal e/ou sintoma de intolerância ao esforço. CONCLUSÕES: O exercício realizado foi eficaz, pois promoveu alterações hemodinâmicas e na modulação autonômica nesses pacientes, sem ocasionar qualquer intercorrência clínica.