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Background: Refractory cardiogenic shock (CS) is associated with high mortality rates, and the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a therapeutic option has generated discussions. Therefore, its cost-effectiveness, especially in low- and middle-income countries like Brazil, remains uncertain.Objectives: To conduct a cost-utility analysis from the Brazilian Unified Health System perspective to assess the cost-effectiveness of VA-ECMO combined with standard care compared to standard care alone in adult refractory CS patients., Methods: We followed a cohort of refractory CS patients treated with VA-ECMO in tertiary care centers located in Southern Brazilian. We collected data on hospital outcomes and costs. We conducted a systematic review to supplement our data and utilized a Markov model to estimate incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) and per life-year gained., Results: In the base-case analysis, VA-ECMO yielded an ICER of Int$ 37,491 per QALY. Sensitivity analyses identified hospitalization cost, relative risk of survival, and VA-ECMO group survival as key drivers of results. Probabilistic sensitivity analysis favored VA-ECMO, with a 78% probability of cost-effectiveness at the recommended willingness-to-pay threshold., Conclusions: Our study suggests that, within the Brazilian Health System framework, VA-ECMO may be a cost-effective therapy for refractory CS. However, limited efficacy data and recent trials questioning its benefit in specific patient subsets highlight the need for further research. Rigorous clinical trials, encompassing diverse patient profiles, are essential to confirm cost-effectiveness and ensure equitable access to advanced medical interventions within healthcare systems, particularly in socio-economically diverse countries like Brazil.

Background: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America., Methods: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated., Results: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months., Conclusions: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sudden cardiac death (SCD) is an unpredictable and common mode of death in patients with heart failure (HF). Alterations in calcium handling may lead to malignant arrhythmias, resulting in SCD, and variants in calcium signaling-related genes have a significant association with SCD. Therefore, the aim of the present retrospective cohort study was to investigate the association of Ser96Ala [histidine-rich calcium-binding protein ( HRC )], Ser49Gly [β1-adrenergic receptor ( ADRB1 )], Arg389Gly ( ADRB1 ) and Gly1886Ser [ryanodine receptor 2 ( RYR2 )] polymorphisms with serious arrhythmic events and overall mortality in patients with HF with reduced left ventricular ejection fraction of non-ischemic etiology. In total, 136 patients with HF underwent physical examination, routine laboratory tests, non-invasive assessment of cardiac function and an invasive electrophysiological study. The primary outcome was the occurrence of serious arrhythmic events, set as either SCD or appropriate implantable cardioverter-defibrillator (ICD) therapy, and the secondary outcome was all-cause death. During a median follow-up of 37 months, arrhythmic events occurred in 26 patients (19%) and 41 patients (30%) died. Patients carrying the Ser allele of the Ser96Ala polymorphism in HRC had worse survival than those with the Ala/Ala genotype (log-rank P=0.043). Despite the difference in survival time, the Ala/Ala genotype was not associated with all-cause death in the regression analysis [unadjusted hazard ratio (HR)=0.17; 95% CI, 0.02-1.21]. Regarding the Ser49Gly and Arg389Gly polymorphisms in ADRB1 , homozygosity for the major alleles at both sites (Ser49Ser and Arg389Arg) was associated with a two-fold increased risk of all-cause death compared with the other genotype combinations (unadjusted HR=1.98; 95% CI, 1.02-3.82). However, this association was lost after controlling for clinical covariates. No association was observed for the Gly1886Ser polymorphism in RYR2 . Overall, the present findings are concurrent with the hypothesis that the Ser96Ala ( HRC ), Ser49Gly ( ADRB1 ) and Arg389Gly ( ADRB1 ) polymorphisms may be associated with HF prognosis. In particular, the Ser96Ala polymorphism might aid in risk stratification and patient selection for ICD implantation., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Telles et al.)

Diastolic dysfunction (DD) is routinely evaluated in echocardiography to support diagnosis, prognostication, and management of heart failure, a condition highly prevalent in elderly patients. Clinical guidelines were published in 2009, and updated in 2016, pursuing to standardize and improve DD categorization. We aimed to assess the concordance of DD between these two documents in an elderly population and to investigate how left ventricular structural abnormalities (LVSA) impact the reclassification. To evaluate this we analyzed the 308 consecutive transthoracic echocardiograms in patients older than 60 years (70.4 ± 7.7 years-old, 59% women) that fulfilled the inclusion criteria out of the 1438 echocardiograms performed in a tertiary hospital. We found that the prevalence of DD was lower according to the 2016 criteria (64% vs. 91%; p < 0.001), with 207 (67.2%) patients changing category, indicating poor agreement between the guidelines (kappa = 0.21). There were 188 (61%) patients with LVSA, which drove most of the reclassifications in 2016 Grade I DD cases. The prevalence of elevated filling pressures by Doppler halved in this elderly population using the updated recommendations (20.9% vs. 39.2%; p < 0.001). In conclusion the prevalence of DD was lower applying the 2016 guidelines, with a poor agreement with 2009 guidelines in all DD grades. The role of LVSA in reclassifications was particularly evident in Grade I DD, while Doppler parameters drove reclassifications among the more severe grades. If not properly addressed, these discrepancies may undermine the reliance on DD as a diagnostic and prognostic tool, particularly in an elderly population at a higher risk of heart failure., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Central Illustration : Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study LVEF: left ventricular ejection fraction; HR: hazard ratio; CI: confidence interval; NYHA: New York Heart Association; VO 2: oxygen consumption., Background: The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF)., Objective: To investigate the prognostic value of the NYHA classification in addition to Weber class., Methods: Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant., Results: A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality., Conclusions: Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Aims: In this multicentre study, we compared cardio-pulmonary exercise test (CPET) parameters between heart failure (HF) patients classified as New York Heart Association (NYHA) class I and II to assess NYHA performance and prognostic role in mild HF., Methods and Results: We included consecutive HF patients in NYHA class I or II who underwent CPET in three Brazilian centres. We analysed the overlap between kernel density estimations for the per cent-predicted peak oxygen consumption (VO 2 ), minute ventilation/carbon dioxide production (VE/VCO 2 ) slope, and oxygen uptake efficiency slope (OUES) by NYHA class. Area under the receiver-operating characteristic curve (AUC) was used to assess the capacity of per cent-predicted peak VO 2 to discriminate between NYHA class I and II. For prognostication, time to all-cause death was used to produce Kaplan-Meier estimates. Of 688 patients included in this study, 42% were classified as NYHA I and 58% as NYHA II, 55% were men, and mean age was 56 years. Median global per cent-predicted peak VO 2 was 66.8% (IQR 56-80), VE/VCO 2 slope was 36.9 (31.6-43.3), and mean OUES was 1.51 (±0.59). Kernel density overlap between NYHA class I and II was 86% for per cent-predicted peak VO 2 , 89% for VE/VCO 2 slope, and 84% for OUES. Receiving-operating curve analysis showed a significant, albeit limited performance of per cent-predicted peak VO 2 alone to discriminate between NYHA class I vs. II (AUC 0.55, 95% CI 0.51-0.59, P = 0.005). Model accuracy for probability of being classified as NYHA class I (vs. NYHA class II) across the spectrum of the per cent-predicted peak VO 2 was limited, with an absolute probability increment of 13% when per cent-predicted peak VO 2 increased from 50% to 100%. Overall mortality in NYHA class I and II was not significantly different (P = 0.41), whereas NYHA class III patients displayed a distinctively higher death rate (P < 0.001)., Conclusions: Patients with chronic HF classified as NYHA I overlapped substantially with those classified as NYHA II in objective physiological measures and prognosis. NYHA classification may represent a poor discriminator of cardiopulmonary capacity in patients with mild HF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Treatment with mechanical circulatory support (MCS) has been proposed to mitigate mortality in cardiogenic shock (CS). However, there is a lack of data on MCS programs implementation and the effect of the learning curve on its outcomes in limited resources countries such as Brazil., Methods: Prospective cohort of patients with CS admitted in four tertiary-care centers treated with Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Clinical outcomes were peri-procedural complications, short-term mortality rate, and the centers' learning curve. The cohort was divided into two periods: from April 2017 to July 2018 ( n  = 24), and from August 2018 to December 2020 ( n  = 25)., Results: The study enrolled 49 patients [age 59 (43-63) years; 34 (70%) males]. The most common causes for CS were acute myocardial infarction in 22 (45%) and acute decompensation of chronic heart failure in 10 (20%). VA-ECMO was employed in 35 (71%) and Impella CP in 14 (29%) of patients. Overall complications occurred in 37 (76%) of patients, where major bleeding in 19 (38%) was the most common. The overall mortality rate was 61%, but it was lower in the second period (40%) in comparison to the first period (83%), p  = 0.002. The learning curve analysis showed a decrease in the mortality rate after 40 consecutive cases., Conclusions: Implementation of a temporary MCS program for refractory CS in a limited resource country is feasible. The learning curve effect might have played a role on survival rate since high morbimortality has decreased within time reaching optimal results by the end of the study.

Background: Risk stratification remains clinically challenging in patients with heart failure (HF) of non-ischemic etiology. Galectin-3 is a serum marker of fibrosis that might help in prognostication., Objective: To determine the role of galectin-3 as a predictor of major arrhythmic events and overall mortality., Methods: We conducted a prospective cohort study that enrolled 148 non-ischemic HF patients. All patients underwent a comprehensive baseline clinical and laboratory assessment, including levels of serum galectin-3. The primary outcome was the occurrence of arrhythmic syncope, appropriate implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, or sudden cardiac death. The secondary outcome was all-cause death. For all statistical tests, a two-tailed p-value<0.05 was considered significant., Results: In a median follow-up of 941 days, the primary and secondary outcomes occurred in 26 (17.5%) and 30 (20%) patients, respectively. Serum galectin-3>22.5 ng/mL (highest quartile) did not predict serious arrhythmic events (HR: 1.98, p=0.152). Independent predictors of the primary outcome were left ventricular end-diastolic diameter (LVEDD)>73mm (HR: 3.70, p=0.001), exercise periodic breathing (EPB) on cardiopulmonary exercise testing (HR: 2.67, p=0.01), and non-sustained ventricular tachycardia (NSVT)>8 beats on Holter monitoring (HR: 3.47, p=0.027). Predictors of all-cause death were galectin-3>22.5 ng/mL (HR: 3.69, p=0.001), LVEDD>73mm (HR: 3.35, p=0.003), EPB (HR: 3.06, p=0.006), and NSVT>8 beats (HR: 3.95, p=0.007). The absence of all risk predictors was associated with a 91.1% negative predictive value for the primary outcome and 96.6% for total mortality., Conclusions: In non-ischemic HF patients, elevated galectin-3 levels did not predict major arrhythmic events but were associated with total mortality. Absence of risk predictors revealed a prevalent subgroup of HF patients with an excellent prognosis.

In the last years, several diagnostic and prognostic biomarkers have been studied in cardiovascular disease. Growth differentiation factor-15 (GDF-15), a cytokine belonging to the transforming growth factor- (TGF-) family, is highly up-regulated in stress and inflammatory conditions and has been correlated to myocardial injury and pressure cardiac overload in animal models. This new biomarker has been positively correlated with increased risk of cardiovascular events in population studies and shown an independent predictor of mortality in patients with coronary artery disease and heart failure. This review aimed to summarize the current evidence on the diagnostic and prognostic value of GDF-15 in different settings in cardiology.

Background: The physical examination enables prognostic evaluation of patients with decompensated heart failure (HF), but lacks reliability and relies on the professional's clinical experience. Considering hemodynamic responses to "fight or flight" situations, such as the moment of admission to the emergency room, we proposed the calculation of the acute hemodynamic index (AHI) from values of heart rate and pulse pressure., Objective: To evaluate the in-hospital prognostic ability of AHI in decompensated HF., Methods: A prospective, multicenter, registry-based observational study including data from the BREATHE registry, with information from public and private hospitals in Brazil. The prognostic ability of the AHI was tested by receiver-operating characteristic (ROC) analyses, C-statistics, Akaike's information criteria, and multivariate regression analyses. p-values < 0.05 were considered statistically significant., Results: We analyzed data from 463 patients with heart failure with low ejection fraction. In-hospital mortality was 9%. The median AHI value was used as cut-off (4 mmHg⋅bpm). A low AHI (≤ 4 mmHg⋅bpm) was found in 80% of deceased patients. The risk of in-hospital mortality in patients with low AHI was 2.5 times that in patients with AHI > 4 mmHg⋅bpm. AHI independently predicted in-hospital mortality in acute decompensated HF (sensitivity: 0.786; specificity: 0.429; AUC: 0.607 [0.540-0.674]; p = 0.010) even after adjusting for comorbidities and medication use [OR: 0.061 (0.007-0.114); p = 0.025)., Conclusions: The AHI independently predicts in-hospital mortality in acute decompensated HF. This simple bed-side index could be useful in an emergency setting. (Arq Bras Cardiol. 2021; 116(1):77-86).

Background: To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP ® ., Methods: Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality., Results: VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67-0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality., Conclusions: Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.

Circulating advanced glycation end products (AGE) and their receptor, RAGE, are increased after a myocardial infarction (MI) episode and seem to be associated with worse prognosis in patients. Despite the increasing importance of these molecules in the course of cardiac diseases, they have never been characterized in an animal model of MI. Thus, the aim of this study was to characterize AGE formation and RAGE expression in plasma and cardiac tissue during cardiac remodeling after MI in rats. Adult male Wistar rats were randomized to receive sham surgery (n = 15) or MI induction (n = 14) by left anterior descending coronary artery ligation. The MI group was stratified into two subgroups based on postoperative left ventricular ejection fraction: low (MIlowEF) and intermediate (MIintermEF). Echocardiography findings and plasma levels of AGEs, protein carbonyl, and free amines were assessed at baseline and 2, 30, and 120 days postoperatively. At the end of follow-up, the heart was harvested for AGE and RAGE evaluation. No differences were observed in AGE formation in plasma, except for a decrease in absorbance in MIlowEF at the end of follow-up. A decrease in yellowish-brown AGEs in heart homogenate was found, which was confirmed by immunodetection of N-ε-carboxymethyl-lysine. No differences could be seen in plasma RAGE levels among the groups, despite an increase in MI groups over the time. However, MI animals presented an increase of 50% in heart RAGE at the end of the follow-up. Despite the inflammatory and oxidative profile of experimental MI in rats, there was no increase in plasma AGE or RAGE levels. However, AGE levels in cardiac tissue declined. Thus, we suggest that the rat MI model should be employed with caution when studying the AGE-RAGE signaling axis or anti-AGE drugs for not reflecting previous clinical findings., Competing Interests: The authors have declared that no competing interests exist.

Objective: Estimate the cost-effectiveness of a nurse-led home visit (HV) intervention as compared with the standard HF management, within a randomized clinical trial in Brazil., Study Design: Cost-effectiveness study within a randomized trial., Methods: To assess the cost-effectiveness of four home visits and four telephone calls by nurses in the management of patients with HF within a randomized clinical trial (RCT: NCT01213875) in a perspective Public (PHS-Public Healthcare System) and private healthcare systems of Brazil during time frame of 24 weeks. The outcome was a composite endpoint hospital readmission rate (first visit to the emergency room (ER) and hospital readmission), or all-cause death and incremental cost-effectiveness ratio (ICER) of the study intervention to conventional management., Results: Home-based intervention was associated with a reduction in composite endpoint (RR 0.73; 95% confidence interval 0.54 - 0.99; P = 0.049), but at greater cost from the PHS perspective. The ICER at 24 weeks was R$585 per hospital readmission visit prevented. Within the private health insurance framework, home visits were associated with lower costs and lower readmission rates. Results were sensitive to the relative risk of the study intervention, admissions and intervention costs., Conclusions: In Brazil, an intervention based on nurse-led home visits of patients with HF showed a favorable cost-effectiveness profile within the framework of the PHS and was dominant within the private healthcare system. Our analysis suggests that implementation of this program could not only benefit patients, but also provide a financial incentive to health administrators., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Clinical studies demonstrate that up to 40% of patients do not respond to cardiac resynchronization therapy (CRT), thus, appropriate patient selection is critical to the success of CRT in heart failure., Objective: Evaluation of mortality predictors and response to CRT in the Brazilian scenario., Methods: Retrospective cohort study including patients submitted to CRT in a tertiary hospital in southern Brazil from 2008 to 2014. Survival was assessed through a database of the State Department of Health (RS). Predictors of echocardiographic response were evaluated using Poisson regression. Survival analysis was performed by Cox regression and Kaplan Meyer curves. A two-tailed p value less than 0.05 was considered statistically significant., Results: A total of 170 patients with an average follow-up of 1011 ± 632 days were included. The total mortality was 30%. The independent predictors of mortality were age (hazard ratio [HR] of 1.05, p = 0.027), previous acute myocardial infarction (AMI) (HR of 2.17, p = 0.049) and chronic obstructive pulmonary disease (COPD) (HR of 3.13, p = 0.015). The percentage of biventricular stimulation at 6 months was identified as protective factor of mortality ([HR] 0.97, p = 0.048). The independent predictors associated with the echocardiographic response were absence of mitral insufficiency, presence of left bundle branch block and percentage of biventricular stimulation., Conclusion: Mortality in patients submitted to CRT in a tertiary hospital was independently associated with age, presence of COPD and previous AMI. The percentage of biventricular pacing evaluated 6 months after resynchronizer implantation was independently associated with improved survival and echocardiographic response.

Introduction: Spontaneous coronary artery dissection is a sudden separation between the layers of a coronary artery wall, non-iatrogenic or trauma related, that has been recognized as an important cause of myocardial infarction., Objective: To report an emblematic case, in terms of angiographic images, clinical presentation and predisposing factors, whose clinical management failure led to surgical intervention., Methods: A previously healthy 48-year-old male farmer was admitted to the emergency room complaining of anterior chest pain described as "tearing", which started after physical exertion. Anterior wall ST-segment depression was observed in the electrocardiogram and troponin levels were increased. The patient then underwent coronary catheterization. Angiography showed a tortuous left anterior descending coronary artery with a dissection line involving proximal and middle segments, resulting in mild to moderate luminal stenosis. At first, a conservative approach was chosen. Control cardiac catheterization, 3 months later, showed dissection progression to the distal segment., Results: The patient was referred to surgical treatment. Internal thoracic artery and a great saphenous vein graft were used to revascularize the target vessels. He had an uneventful postoperative course., Conclusion: In this report, we describe a typical clinical manifestation of an uncommon cause of acute myocardial infarction. The dissection was started by an extreme physical effort, which is a known triggering factor. Management of these cases is always challenging because there are no evidence-based therapies or guideline-based recomendations.

Background: Although heart failure (HF) has high morbidity and mortality, studies in Latin America on causes and predictors of in-hospital mortality are scarce. We also do not know the evolution of patients with compensated HF hospitalized for other reasons., Objective: To identify causes and predictors of in-hospital mortality in patients hospitalized for acute decompensated HF (ADHF), compared to those with HF and admitted to the hospital for non-HF related causes (NDHF)., Methods: Historical cohort of patients hospitalized in a public tertiary hospital in Brazil with a diagnosis of HF identified by the Charlson Comorbidity Index (CCI)., Results: A total of 2056 patients hospitalized between January 2009 and December 2010 (51% men, median age of 71 years, length of stay of 15 days) were evaluated. There were 17.6% of deaths during hospitalization, of which 58.4% were non-cardiovascular (63.6% NDHF vs 47.4% ADHF, p = 0.004). Infectious causes were responsible for most of the deaths and only 21.6% of the deaths were attributed to HF. The independent predictors of in-hospital mortality were similar between the groups and included: age, length of stay, elevated potassium, clinical comorbidities, and CCI. Renal insufficiency was the most relevant predictor in both groups., Conclusion: Patients hospitalized with HF have high in-hospital mortality, regardless of the primary reason for hospitalization. Few deaths are directly attributed to HF; Age, renal function and levels of serum potassium, length of stay, comorbid burden and CCI were independent predictors of in-hospital death in a Brazilian tertiary hospital.

Objectives: The aim of this research is to evaluate the relative cost-effectiveness of functional and anatomical strategies for diagnosing stable coronary artery disease (CAD), using exercise (Ex)-ECG, stress echocardiogram (ECHO), single-photon emission CT (SPECT), coronary CT angiography (CTA) or stress cardiacmagnetic resonance (C-MRI)., Setting: Decision-analytical model, comparing strategies of sequential tests for evaluating patients with possible stable angina in low, intermediate and high pretest probability of CAD, from the perspective of a developing nation's public healthcare system., Participants: Hypothetical cohort of patients with pretest probability of CAD between 20% and 70%., Primary and Secondary Outcome Measures: The primary outcome is cost per correct diagnosis of CAD. Proportion of false-positive or false-negative tests and number of unnecessary tests performed were also evaluated., Results: Strategies using Ex-ECG as initial test were the least costly alternatives but generated more frequent false-positive initial tests and false-negative final diagnosis. Strategies based on CTA or ECHO as initial test were the most attractive and resulted in similar cost-effectiveness ratios (I$ 286 and I$ 305 per correct diagnosis, respectively). A strategy based on C-MRI was highly effective for diagnosing stable CAD, but its high cost resulted in unfavourable incremental cost-effectiveness (ICER) in moderate-risk and high-risk scenarios. Non-invasive strategies based on SPECT have been dominated., Conclusions: An anatomical diagnostic strategy based on CTA is a cost-effective option for CAD diagnosis. Functional strategies performed equally well when based on ECHO. C-MRI yielded acceptable ICER only at low pretest probability, and SPECT was not cost-effective in our analysis., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Heart failure is an increasingly prevalent disease associated with high morbidity and mortality. In 30-40% of patients, the etiology is non-ischemic. In this group of patients, the implantable cardioverter-defibrillator (ICD) prevents sudden death and decreases total mortality. However, due to burden of cost, the fact that many ICD patients will never need any therapy, and possible complications involved in implant and follow-up, the device should not be implanted in every patient with non-ischemic heart failure. There is an urgent need to adequately identify patients with highest sudden death risk, in whom the implant is most cost-effective. In the present paper, the authors discuss current available tests for risk stratification of sudden cardiac death in patients with non-ischemic heart failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: MicroRNAs (miRs) regulate processes involved in both cardiac remodeling and obesity. We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity., Methods: In this case-control study, we compared plasma levels of miR-21, -130b, -221, -423-5p, and the -221/-130b ratio in 57 age- and gender-matched subjects: 40 HF patients (20 obese HF and 20 lean HF) and 17 lean healthy controls. Body composition was estimated by bioelectrical impedance analysis. MiRs were measured by quantitative reverse transcription-PCR. Bioinformatics analysis was performed based on miRs findings to predict their putative targets and investigate their biological function., Results: HF was associated with increased miR-423-5p levels in both lean and obese patients (P<0.05 vs. controls) without differences between HF groups. MiR-130b levels were reduced in obese HF patients compared with HF lean (P=0.036) and controls (P=0.025). MiR-221 levels were non-significantly increased in obese HF patients. MiR-21 levels were not different among the groups. MiR-221/-130b ratio was increased in obese HF patients, and was positively associated with body fat percentage (r=0.43; P=0.002), body mass index (r=0.44; P=0.002), and waist circumference (r=0.40; P=0.020). Computational prediction of target genes followed by functional enrichment analysis indicated a relevant role of miR-130b and miR-221 in modulating the expression of genes associated to cardiovascular and endocrine diseases, and suggested their influence in important signaling mechanisms and in numerous processes related to the circulatory and endocrine systems., Conclusions: In HF patients, the presence of obesity is associated with a differential expression of selected miRs and the miR-221/-130b ratio had significant correlations with adiposity parameters. Computational target prediction analysis identified several interrelated pathways targeted by miR-130b and miR-221 with a known relationship with endocrine and cardiovascular diseases, representing potential mechanisms to be further validated., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Despite significant therapeutic advancements, heart failure remains a highly prevalent clinical condition associated with significant morbidity and mortality. In 30%-40% patients, the etiology of heart failure is nonischemic. The implantable cardioverter-defibrillator (ICD) is capable of preventing sudden death and decreasing total mortality in patients with nonischemic heart failure. However, a significant number of patients receiving ICD do not receive any kind of therapy during follow-up. Moreover, considering the situation in Brazil and several other countries, ICD cannot be implanted in all patients with nonischemic heart failure. Therefore, there is an urgent need to identify patients at an increased risk of sudden death because these would benefit more than patients at a lower risk, despite the presence of heart failure in both risk groups. In this study, the authors review the primary available methods for the stratification of the risk of sudden death in patients with nonischemic heart failure.

Aims: Home-based interventions for heart failure (HF) patients might be particularly effective in middle-income countries, where social, cultural, and economic constraints limit the effectiveness of HF treatment outside the hospital environment., Methods and Results: HELEN-II was a randomized clinical trial conducted in Brazil designed to evaluate the clinical efficacy of a nurse-based strategy, started after discharge following an acute decompensated HF (ADHF) admission. HELEN-II compares the efficacy of home visits and telephone reinforcement (n = 123) with that of the conventional strategy, which is based on medical follow-up (n = 129). The primary outcome was a composite endpoint of a first visit to the emergency department (≤ 24 h), a hospital readmission (> 24 h), or all-cause death, assessed during the first 6 months of follow-up. Most enrolled subjects were middle-aged (62 ± 13 years) males (63%) in NYHA functional class II-III (84%) with severe LV dysfunction (mean LVEF 29.6 ± 9%). The primary composite endpoint was decreased by 27% in the interventional group (relative risk 0.73; 95% confidence interval 0.54-0.99; P = 0.049). At the end of follow-up, the rate of use of the standard-of-care HF medications was similar in both groups, except for the higher use of furosemide in the interventional group. Also, HF knowledge and self-care were significantly increased in the interventional group., Conclusions: A post-discharge, nurse-led management strategy significantly decreases the morbidity of ADHF patients in the public health system of a developing middle-income country., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

There is a very well known correlation between diabetes and cardiovascular disease but many health care professionals are just concerned with glycemic control, ignoring the paramount importance of controlling other risk factors involved in the pathogenesis of serious cardiovascular diseases. This Position Statement from the Brazilian Diabetes Society was developed to promote increased awareness in relation to six crucial topics dealing with diabetes and cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension, Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be the best algorithm for the use of statins in diabetic patients received a special attention and a new Brazilian algorithm was developed by our editorial committee. This document contains 38 recommendations which were classified by their levels of evidence (A, B, C and D). The Editorial Committee included 22 specialists with recognized expertise in diabetes and cardiology.

Context: Matrix metalloproteinases are involved in atherosclerosis and plaque vulnerability., Objective: To investigate serum levels and genetic polymorphisms of matrix metalloproteinases (MMPs) -1, -3 and -9 in patients submitted to carotid endarterectomy., Methods: Genetic polymorphisms were evaluated using polymerase chain reaction (PCR-RFLP); serum levels were measured using ELISA; histological sections were stained with Picrosirius Red to analyze the fibrous cap thickness, lipid core and collagen content and with hematoxylin--eosin to detect the presence of intraplaque hemorrhage., Results: MMP-9 serum levels were significantly higher in patients with a thinner fibrous cap (p = 0.033) or acute or recent intraplaque hemorrhage (p = 0.008) on histology, as well as in patients with previous stroke (p = 0.009) or peripheral vascular disease (p = 0.049). No consistent associations were observed between different MMP genotypes and fibrous cap thickness, lipid core, collagen content or intraplaque hemorrhage., Conclusions: MMP-9 serum levels were consistently associated with markers of carotid atherosclerosis and lesion vulnerability, whereas specific MMP genotypes were not.

Background: Most reports regarding the obesity paradox have focused on body mass index (BMI) to classify obesity and the prognostic values of other indirect measurements of body composition remain poorly examined in heart failure (HF)., Objective: To evaluate the association between BMI and other indirect, but easily accessible, body composition measurements associated with the risk of all-cause mortality in HF., Methods: Anthropometric parameters of body composition were assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of <50% from a prospective HF cohort that was followed-up for 30 ± 8.2 months. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis., Results: HF patients were predominantly male, of non-ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 ± 9%). Triceps skinfold (TSF) was the only anthropometric index that was associated with HF prognosis and had significantly lower values in patients who died (p = 0.047). A TSF > 20 mm was present in 9% of patients that died and 22% of those who survived (p = 0.027). Univariate analysis showed that serum creatinine level, LVEF, and NYHA class were associated with the risk of death, while Cox proportional hazard regression analysis showed that TSF > 20 was a strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95% confidence interval = 0.13-0.97, p = 0.03)., Conclusion: Although BMI is the most widely used anthropometric parameter in clinical practice, our results suggested that TSF is a better predictive marker of mortality in HF outpatients.

Background: Metabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects., Objectives: Compare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls., Methods: MS patients (n = 76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP)., Results: MS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng/mL vs. 330.4 ± 162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS., Conclusion: MS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.

Aims: Evaluating myocardial infarct (MI) size prior to intervention is fundamental to ensure accurate results in experimental studies. However, this assessment is performed at late time points. We aimed to evaluate whether measuring plasma cardiac troponin I (cTnI) and performing echocardiographic assessment at earlier time points can predict the occurrence of MI and infarct size., Main Methods: Male Wistar rats were subjected to MI (n=40) or sham surgery (n=11). cTnI levels were measured 2 and 8h after MI. Echocardiographic evaluations were performed at 48h and 14days post-MI. After 14days, the animals were euthanized, and the hearts were removed and paraffin-embedded for Sirius red staining., Key Findings: cTnI plasma levels increased in the MI group relative to the sham group at 2h after MI (7.2±9.4ng/mL vs. 2.3±1.0ng/mL; p<0.01) with a further increase at 8h after MI (22.2±13.5ng/mL vs. 1.5±1.7ng/mL; p<0.001). cTnI levels (8h) and echocardiographic outcomes correlated with histological infarct size 14days after MI (r=0.74, p<0.001 and r=0.84, p<0.001, respectively), but only echocardiography could confidently identify small, medium, and large infarcts. Additionally, using a cutoff value of 4.8ng/mL we achieved 100% specificity and 91% sensitivity in detecting MI., Significance: A cutoff value of 4.8ng/mL for cTnI could be used as early as 8h after MI to accurately identify infarct in this model, whereas echocardiographic images taken 48h after MI predicted the infarcted area 14days after MI., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We performed a cost-effectiveness study of different strategies of screening for cardiotoxicity in patients receiving imatinib, the first strategy based on yearly echocardiograms in all patients and the second strategy based on yearly B-type natriuretic peptide level measurement, reserving echocardiograms for patients with an abnormal test result. Results are presented in terms of additional cost per diagnosis as compared with not performing any screening. From the Brazilian private sector's perspective, strategies 1 and 2 resulted in additional costs of US $30,951.53 and US $19,925.64 per diagnosis of cardiotoxicity, respectively. From the perspective of the Brazilian public health system, the same strategies generated additional costs of US $7,668.00 and US $20,232.87 per diagnosis, respectively. In our study, systematic screening for cardiotoxicity in patients using imatinib has a high cost per diagnosis. If screening is to be adopted, a strategy based on B-type natriuretic peptide level measurement, reserving echocardiography for patients with abnormal results, results in lower costs per diagnosis in the private sector. From the public health system's perspective, costs per diagnosis will greatly depend on the reimbursement values adopted for B-type natriuretic peptide level measurement., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: The loss of viable myocardium subsequent to myocardial infarction (MI) impairs cardiac function, and oxidative stress is considered to be critical in this process., Objectives: To assess cardiac function and correlate it with oxidative stress and antioxidant levels in cardiac tissue at 48 h post-MI., Methods: Adult male Wistar rats (n=6 per group) with a mean (± SD) weight of 229±24 g were randomly assigned to either an infarcted group or a control group. MI was induced by occlusion of the left coronary artery. Cardiac function was evaluated by measuring left ventricular (LV) ejection fraction, LV fractional shortening, cardiac output, myocardial performance index and the peak early diastolic velocity/peak atrial velocity ratio using echocardiography. The myocardial oxidative stress profile was assessed by measuring the reduced glutathione/oxidized glutathione ratio, H2O2 levels, peroxiredoxin-6 protein levels and activity levels of superoxide dismutase, catalase and glutathione peroxidase. Lipid peroxidation was quantified using chemiluminescence, and protein oxidation was determined by measuring protein carbonyl levels., Results: LV ejection fraction and LV fractional shortening were lower in the infarcted group compared with the sham group, whereas the peak early diastolic velocity/peak atrial velocity ratio and myocardial performance index were significantly increased, indicating systolic dysfunction. Lipid peroxidation, protein carbonyls and superoxide dismutase and catalase activity levels did not differ between the groups. Peroxyredoxin-6 levels were increased in the infarcted group, while H2O2 levels were reduced. The reduced glutathione/oxidized glutathione ratio and the glutathione peroxidase activity were reduced in the infarcted group compared with control., Discussion and Conclusion: These data suggest that MI-induced cardiac dysfunction and impaired redox balance may be associated with the activation of counter-regulatory responses to maintain reduced H2O2 concentrations and, thereby, prevent further oxidative damage at this early time point.

Purpose: Noninvasive evaluation of endothelial function may be accomplished by ultrasound assessment of flow-mediated vasodilation (FMD) of the brachial artery. This study aims to investigate the role of FMD analysis on intrahospital prognosis of patients with sepsis., Methods: Adult patients admitted to the intensive care unit with severe sepsis or septic shock were consecutively included. Brachial artery FMD was measured upon admission, after 24 and 72 hours. A group of apparently healthy subjects paired for sex and age was used as controls. Patients were followed up to discharge or death., Results: We studied 42 patients (mean age, 51 ± 19 years) with sepsis predominantly of abdominal or respiratory etiology (75%). Acute Physiology And Chronic Health Evaluation II risk score was 23 ± 7, and intrahospital mortality rate was 33%. Flow-mediated vasodilation in septic patients was significantly lower than in healthy controls (1.5 ± 7% vs 6 ± 4%, P < .001). Most of the nonsurvivors (86%) showed a decline in sequential FMD analyses, whereas only 43% of survivors showed a reduction of FMD (P = .01). In nonsurvivors, FMD was significantly lower 72 hours after sepsis onset (-3.3% ± 10% vs 5.2% ± 4%; P < .05; time-group interaction P value = .03)., Conclusions: Brachial FMD is altered in septic patients with hemodynamic instability, and its deterioration may be an early marker of unfavorable prognosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate echocardiography-based indices of myocardial function and markers of vascular inflammation and endothelial dysfunction in the early phases of severe sepsis., Material and Methods: Forty-five adult patients (67% women; age 51 ± 18 years; Acute Physiology and Chronic Health Disease Classification System II score, 23 ± 7) admitted to the intensive care unit up to 24 hours after fulfilling criteria for severe sepsis or septic shock were studied. Clinical, laboratorial (endothelin 1 [ET1], vascular cellular adhesion molecule 1), and echocardiographic data were collected within the first 24 hours and again 72 hours and 7 days after admission., Results: Intrahospital mortality was 33% (15 deaths). Left ventricular (LV) dysfunction (LV ejection fraction <55%) was identified in 15 (33%) patients, whereas right ventricular (RV) dysfunction (RV tissue Doppler peak systolic velocity [RV-Sm] <12 cm/s) was present in 14 (30%) patients. LogET1 was increased in patients with LV dysfunction (2.3 ± 0.6 vs 1.8 ± 0.4 pg/mL; P = .01) and RV dysfunction (2.5 ± 0.5 vs 1.8 ± 0.4 pg/mL; P < .001) and had negative correlations with LV ejection fraction (r = -0.50; P = .002) and RV-Sm (r = -0.67; P < .001). Left ventricular end-diastolic diameter, RV-Sm, and diastolic dysfunction were able to discriminate survivors from nonsurvivors, and the combination of these parameters identified groups of very low and high risk., Conclusion: Both LV and RV systolic dysfunctions are prevalent in severe sepsis, being directly associated with markers of endothelial dysfunction. Left ventricular nondilation, RV dysfunction, and diastolic dysfunction seem related to poor prognosis in this scenario., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background and Purpose: To investigate early vascular changes related to carotid atherosclerotic injury post-radiation therapy (RT), we studied carotid intima-media thickness (IMT) and vascular cellular adhesion molecule (VCAM)-1 at two time-points after RT and compared local and remote irradiation effects in patients with head and neck (HNC) and prostate cancer (PC), respectively., Material and Methods: We prospectively studied patients beginning RT for HNC or PC, performing carotid ultrasound before RT, early after and six months after treatment to measure carotid IMT. Blood samples were simultaneously collected to study VCAM-1 by ELISA., Results: We studied 19 patients with HNC and 24 with PC. Patients with HNC were younger (55 ± 10 years) than PC patients (68 ± 8 years). Early post-RT only HNC patients had an increase in IMT compared to baseline measurements (0.73 ± 0.04 mm vs. 0.80 ± 0.05 mm, p=0.029). On the other hand, VCAM-1 levels decreased in PC patients, remaining unchanged in HNC patients. Late post-RT (six months from previous assessment), neither IMT nor VCAM-1 values changed in both groups., Conclusion: Local and remote RT seem to exert differential early effects regarding vascular-related changes: (1) local RT seems to affect vascular structure and increase IMT and (2) RT for PC is associated with reduction in VCAM levels, suggesting systemic modulation of cancer-related factors., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The recent publication of the MADIT-CRT and RAFT trials has more than doubled the number of patients in which a direct comparison of the combination of cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) versus ICD alone was carried out. The present meta-analysis aims to assess the impact of combined CRT and ICD therapy on survival of heart failure (HF) patients., Methods and Results: Medline, Embase, and the Cochrane Library databases were searched, and all randomized controlled trials of CRT alone or combined with ICDs in HF resulting from left ventricular systolic dysfunction were included. Main outcome was all-cause mortality. Summary relative risk (RR) and 95% confidence interval (CI) were calculated employing random-effects models. Twelve studies were included, with a total of 8,284 randomized patients. For the comparison of CRT alone versus medical therapy, pooled analysis of 5 available trials demonstrated a significant reduction in all-cause mortality with CRT (RR 0.76, 95% CI: 0.64-0.9). Pooled analysis of 6 trials that compared the combination of CRT and ICD therapy to ICD alone also showed a statistically significant reduction in all-cause mortality (RR 0.83, 95% CI: 0.72-0.96). Stratified analysis showed significant mortality reductions in all New York Heart Association class subgroups, with greater effect in classes III-IV (RR 0.70; 95% CI: 0.57-0.88). Pooled estimates of implant-related risks were 0.6% for death and 8% for implant failure., Conclusion: Combined CRT and ICD therapy reduces overall mortality in HF patients when compared with ICD alone., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: To investigate the influence of polymorphisms in CYP2C9, VKORC1, CYP4F2 and F2 genes on warfarin dose-response and develop a model including genetic and non-genetic factors for warfarin dose prediction needed for each patient., Methods: A total of 279 patients of European ancestry on warfarin medication were investigated. Genotypes for -1639G>A, 1173C>T, and 3730G>A SNPs in the VKORC1 gene, CYP2C9*2 and CYP2C9*3, 1347C>T in the CYP4F2 gene and 494C>T in the F2 gene were determined by allelic discrimination with Taqman 5'-nuclease assays., Results: The CYP2C9*2 and CYP2C9*3 polymorphisms in the CYP2C9 gene, -1639G>A and 1173C>T in the VKORC1 gene and 494C>T in the F2 gene are responsible for lower anticoagulant doses. In contrast, 1347C>T in the CYP4F2 gene and 3730G>A in the VKORC1 gene are responsible for higher doses of warfarin. An algorithm including genetic, biological and pharmacological factors that explains 63.3% of warfarin dose variation was developed., Conclusion: The model suggested has one of the highest coefficients of determination among those described in the literature., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Objective: Exercise therapy in heart failure (HF) patients is considered safe and has demonstrated modest reduction in hospitalization rates and death in recent trials. Previous cost-effectiveness analysis described favorable results considering long-term supervised exercise intervention and significant effectiveness of exercise therapy; however, these evidences are now no longer supported. To evaluate the cost-effectiveness of supervised exercise therapy in HF patients under the perspective of the Brazilian Public Healthcare System., Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratio of supervised exercise therapy compared to standard treatment in patients with New York Heart Association HF class II and III. Effectiveness was evaluated in quality-adjusted life years in a 10-year time horizon. We searched PUBMED for published clinical trials to estimate effectiveness, mortality, hospitalization, and utilities data. Treatment costs were obtained from published cohort updated to 2008 values. Exercise therapy intervention costs were obtained from a rehabilitation center. Model robustness was assessed through Monte Carlo simulation and sensitivity analysis. Cost were expressed as international dollars, applying the purchasing-power-parity conversion rate., Results: Exercise therapy showed small reduction in hospitalization and mortality at a low cost, an incremental cost-effectiveness ratio of Int$26,462/quality-adjusted life year. Results were more sensitive to exercise therapy costs, standard treatment total costs, exercise therapy effectiveness, and medications costs. Considering a willingness-to-pay of Int$27,500, 55% of the trials fell below this value in the Monte Carlo simulation., Conclusions: In a Brazilian scenario, exercise therapy shows reasonable cost-effectiveness ratio, despite current evidence of limited benefit of this intervention., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Context: The relation between endothelial dysfunction (ED), glycemic control, and early type I diabetes mellitus (T1DM) is unclear., Objective: The objective of the study was to evaluate the association of ED, glycemic control, and the duration of diabetes in T1DM., Design: This was a cross-sectional study., Setting: The study was conducted at a public outpatient clinic., Patients: Fifty-seven T1DM adolescents and 10 healthy age-matched controls participated in the study., Intervention: There were no interventions., Methods and Outcome Measures: Endothelial function (ED) was evaluated by flow-mediated dilation (FMD) in the brachial artery after reactive hyperemia. Biochemical data, including HbA1c (glycohemoglobin), high-sensitivity C-reactive protein, lipids, and urinary albumin excretion were collected. Means of four HbA1c values collected at 3-month intervals in the first and second year before FMD analyses were obtained., Results: Mean FMD was decreased in T1DM compared with controls (P = 0.023), independent of age, smoking, hypertension, or dyslipidemia. Twenty-eight of 57 T1DM patients enrolled (49%) had ED. FMD was decreased in microalbuminuric (4.1%) compared with normoalbuminuric patients (10.1%, P = 0.01) and controls (14.6%, P < 0.001). FMD correlated inversely with mean second-year HbA1c (r = -0.426, P = 0.02), particularly in patients with less than 5 yr of T1DM (r = -0.61, P = 0.004). In these patients, high-sensitivity C-reactive protein was strongly correlated with mean first-year HbA1c (r = -0.66, P = 0.0003). In patients with more than 5 yr of T1DM, we found no significant correlations between ED and glycemic control., Conclusions: Endothelial dysfunction is common in T1DM adolescents with less than 5 yr of disease. It is associated with duration of disease, microalbuminuria, and mean second-year HbA1c but not with mean first-year HbA1c. These data support the metabolic memory hypothesis.

Background: Little is known about the immediate outcomes of the Mobile Emergency Medical Services (SAMU) in Brazil., Objective: To evaluate clinical predictors of survival of patients in cardiorespiratory arrest (CRA) in the nonhospital environment treated by the SAMU in the city of Porto Alegre., Methods: The present study has a prospective and observational design. The evaluated outcomes were 30-day survival and hospital discharge, in addition to the Cerebral Performance Category (CPC) score I-II., Results: From January to October 2008, a total of 593 patients in nontraumatic CRA were treated and 260 cardiopulmonary resuscitation (CPR) attempts were made. There was an initial successful outcome in 52 (20.0%) cases, with 16 patients (6.0%) alive on the 30th day and 10 being discharged from the hospital (3.9%), of which 6 (2.3%) presented CPC I-II score. The CPR at home was inversely associated with 30-day survival (p = 0.001) and hospital discharge survival (p = 0.02). An initial "shockable" rhythm (p = 0.008) was associated with 30-day survival. The response-time and collapse-time intervals until CPR start were significantly shorter in 30-day survivors. At multivariate analysis, independent 30-day mortality predictors were an initial shockable rhythm (odds ratio [OR] = 0.28 and 95% confidence interval [95%CI] = 0.10 - 0.81; p = 0.02) and CPR at home (OR = 3.0 and 95CI% = 1.04 - 8.7; p = 0.04)., Conclusion: The pre-hospital care of CRA in the city of Porto Alegre has limited results; however, they are comparable to the results from other international locations. It is necessary to reinforce each link of the survival chain to improve pre-hospital care, aiming at improving clinically relevant outcomes.