Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Focal adhesion kinase governs cardiac concentric hypertrophic growth by activating the AKT and mTOR pathways

The heart responds to sustained overload by hypertrophic growth in which the myocytes distinctly thicken or elongate on increases in systolic or diastolic stress. Though potentially adaptive, hypertrophy itself may predispose to cardiac dysfunction in pathological settings. The mechanisms underlying the diverse morphology and outcomes of hypertrophy are uncertain. Here we used a focal adhesion kinase (FAK) cardiac-specific transgenic mice model (FAK-Tg) to explore the function of this non-receptor tyrosine kinase on the regulation of myocyte growth. FAK-Tg mice displayed a phenocopy of concentric cardiac hypertrophy, reflecting the relative thickening of the individual myocytes. Moreover, FAK-Tg mice showed structural, functional and molecular features of a compensated hypertrophic growth, and preserved responses to chronic pressure overload. Mechanistically, FAK overexpression resulted in enhanced myocardial FAK activity, which was proven by treatment with a selective FAK inhibitor to be required for the cardiac hypertrophy in this model. Our results indicate that upregulation of FAK does not affect the activity of Src/ERK1/2 pathway, but stimulated signaling by a cascade that encompasses PI3K, AKT, mTOR, S6K and rpS6. Moreover, inhibition of the mTOR complex by rapamycin extinguished the cardiac hypertrophy of the transgenic FAK mice. These findings uncover a unique role for FAK in regulating the signaling mechanisms that governs the selective myocyte growth in width, likely controlling the activity of PI3K/AKT/mTOR pathway, and suggest that FAK activation could be important for the adaptive response to increases in cardiac afterload. This article is part of a Special Issue entitled "Local Signaling in Myocytes". (C) 2011 Elsevier Ltd. All rights reserved.

Comparison between multiplanar and rendering modes in the assessment of fetal atrioventricular valve areas by 3D/4D ultrasonography

Objective: To compare the agreement of multiplanar and rendering modes in the assessment fetal atrioventricular valves (mitral and tricuspid) areas by three-dimensional (3D) ultrasonography using the software spatio-temporal image correlation (STIC). Methods: We conducted a prospective cross-sectional study with normal pregnant women, with single fetuses, between 18-33 weeks. To measure the areas, we used the plan of four-chamber view. In the case of multiplanar, the plane was rotated on the axis "Z" form the heart to position at 9h. For rendering, the green line (region of interest - ROI) was placed from the atria of the heart perpendicular to the crux. The agreement was assessed by a Bland-Altman (limits of agreement) using the relative difference between the measures: ((rendering mode) - (multiplanar mode)) / (average). Results: 328 fetuses were evaluated. We have not identified the occurrence of systematic error between methods: the average relative difference was 1.62% (-2.07% to 5.32%, confidence interval 95%) in the mitral and 1.77% (- 1.08% to 4.62%) in the tricuspid valve. The limits of agreement between methods were -65.26% to 68.51% for the mitral and -49.91% to 53.45% for the tricuspid. Conclusions: There was no systematic error between modes and thus the observed values for the area of fetal atrioventricular valves can be used for comparisons needs to be corrected. However, relatively large variations may be observed when repeating the measurement area by different modes.

Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation

Background: The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods: Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results: In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 +/- 0.16 in normal hearts to 0.22 +/- 0.08 in the remote zone of the remodeled hearts (p<0.05). This was confirmed histologically by the reduction of HA in the subepicardium from -52.03 degrees +/- 2.94 degrees in normal hearts to -37.48 degrees +/- 4.05 degrees in the remote zone of the remodeled hearts (p < 0.05). Conclusions: A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors

Systemic administration of cannabidiol (CBD) attenuates cardiovascular and behavioral changes induced by re-exposure to a context that had been previously paired with footshocks. Previous results from our group using cFos immunohistochemistry suggested that the bed nucleus of the stria terminalis (BNST) is involved in this effect. The mechanisms of CBD effects are still poorly understood, but could involve 5-HT1A receptor activation. Thus, the present work investigated if CBD administration into the BNST would attenuate the expression of contextual fear conditioning and if this effect would involve the activation of 5-HT1A receptors. Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (six footshocks, 1.5 mA/3 s). Twenty-four hours later freezing and cardiovascular responses (mean arterial pressure and heart rate) to the conditioning box were measured for 10 min. CBD (15, 30 or 60 nmol) or vehicle was administered 10 min before the re-exposure to the aversive context. The second experiment was similar to the first one except that animals received microinjections of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol) 5 min before CBD (30 nmol) treatment. The results showed that CBD (30 and 60 nmol) treatment significantly reduced the freezing and attenuated the cardiovascular responses induced by re-exposure to the aversive context. Moreover, WAY100635 by itself did not change the cardiovascular and behavioral response to context, but blocked the CBD effects. These results suggest that CBD can act in the BNST to attenuate aversive conditioning responses and this effect seems to involve 5-HT1A receptor-mediated neurotransmission.

Insulin alone or with captopril: effects on signaling pathways (AKT and AMPK) and oxidative balance after ischemia-reperfusion in isolated hearts

Insulin and the inhibition of the reninangiotensin system have independent benefits for ischemiareperfusion injury, but their combination has not been tested. Our aim was to evaluate the effects of insulin+captopril on insulin/angiotensin signaling pathways and cardiac function in the isolated heart subjected to ischemiareperfusion. Isolated hearts were perfused (Langendorff technique) with KrebsHenseleit (KH) buffer for 25 min. Global ischemia was induced (20 min), followed by reperfusion (30 min) with KH (group KH), KH+angiotensin-I (group A), KH+angiotensin-I+captopril (group AC), KH+insulin (group I), KH+insulin+angiotensin-I (group IA), or KH+insulin+angiotensin-I+captopril (group IAC). Group A had a 24% reduction in developed pressure and an increase in end-diastolic pressure vs. baseline, effects that were reverted in groups AC, IA, and IAC. The phosphorylation of protein kinase B (AKT) was higher in groups I and IA vs. groups KH and A. The phosphorylation of AMP-activated protein kinase (AMPK) was similar to 31% higher in groups I, IA, and IAC vs. groups KH, A, and AC. The tert-butyl hydroperoxide (tBOOH)-induced chemiluminescence was lower (similar to 2.2 times) in all groups vs. group KH and was similar to 35% lower in group IA vs. group A. Superoxide dismutase content was lower in groups A, AC, and IAC vs. group KH. Catalase activity was similar to 28% lower in all groups (except group IA) vs. group KH. During reperfusion of the ischemic heart, insulin activates the AKT and AMPK pathways and inhibits the deleterious effects of angiotensin-I perfusion on SOD expression and cardiac function. The addition of captopril does not potentiate these effects.

Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease

Recent studies have identified the genetic underpinnings of a growing number of diseases through targeted exome sequencing. However, this strategy ignores the large component of the genome that does not code for proteins, but is nonetheless biologically functional. To address the possible involvement of regulatory variation in congenital heart diseases (CHDs), we searched for regulatory mutations impacting the activity of TBX5, a dosage-dependent transcription factor with well-defined roles in the heart and limb development that has been associated with the HoltOram syndrome (hearthand syndrome), a condition that affects 1/100 000 newborns. Using a combination of genomics, bioinformatics and mouse genetic engineering, we scanned approximate to 700 kb of the TBX5 locus in search of cis-regulatory elements. We uncovered three enhancers that collectively recapitulate the endogenous expression pattern of TBX5 in the developing heart. We re-sequenced these enhancer elements in a cohort of non-syndromic patients with isolated atrial and/or ventricular septal defects, the predominant cardiac defects of the HoltOram syndrome, and identified a patient with a homozygous mutation in an enhancer approximate to 90 kb downstream of TBX5. Notably, we demonstrate that this single-base-pair mutation abrogates the ability of the enhancer to drive expression within the heart in vivo using both mouse and zebrafish transgenic models. Given the population-wide frequency of this variant, we estimate that 1/100 000 individuals would be homozygous for this variant, highlighting that a significant number of CHD associated with TBX5 dysfunction might arise from non-coding mutations in TBX5 heart enhancers, effectively decoupling the heart and hand phenotypes of the HoltOram syndrome.

Salivary Cortisol, Alpha-Amylase and Heart Rate Variation in Response to Dental Treatment in Children

Objective. Anxiety and stress are usually related to the dental treatment situation. The objective was to investigate salivary cortisol and alpha-amylase levels (salivary biomarkers) and heart rate in children undergoing a minor dental procedure (dental prophylaxis). Study design. In total, 31 children (range 84-95 months) of both genders without caries or history of dental treatment/pain/trauma were selected. Three saliva samples were gathered: one prior to dental prophylaxis, one immediately after, and one ten minutes later Weight and height were assessed, and heart rate was evaluated prior to and during the procedure. Data were analyzed by correlation tests and t-test/Wikoxon (alpha=0.05). Results. Higher cortisol and amylase levels were observed before prophylaxis compared to afterward. Cortisol and amylase levels did not show a significant correlation, nor did salivary biomarkers and body mass index. However, heart rate and amylase levels showed a significant positive correlation. Conclusions. In the studied sample, certain anticipation of the dental treatment was observed because higher cortisol and amylase levels were observed before, rather than after, the event; moreover, a significant correlation between amylase levels and heart rate was observed. Thus, salivary biomarkers may be a valuable tool for evaluating anxiety-producing events, such as dental treatment, in children.

Using exercise training to counterbalance chronotropic incompetence and delayed heart rate recovery in systemic lupus erythematosus: a randomized trial

Objective. To evaluate the efficacy of a 3-month exercise training program in counteracting the chronotropic incompetence and delayed heart rate recovery in patients with systemic lupus erythematosus (SLE). Methods. A 12-week randomized trial was conducted. Twenty-four inactive SLE patients were randomly assigned into 2 groups: trained (T; n = 15, 3-month exercise program) and nontrained (NT; n = 13). A sex-, body mass index-, and age-matched healthy control (C) group (n = 8) also underwent the exercise program. Subjects were assessed at baseline and at 12 weeks after training. Main measurements included the chronotropic reserve (CR) and the heart rate (HR) recovery (Delta HRR) as defined by the difference between HR at peak exercise and at both the first (Delta HRR1) and second (Delta HRR2) minutes after the exercise test. Results. Neither the NT SLE patients nor the C group presented any change in the CR or in Delta HRR1 and Delta HRR2 (P > 0.05). The exercise training program was effective in promoting significant increases in CR (P = 0.007, effect size [ES] 1.15) and in Delta HRR1 and Delta HRR2 (P = 0.009, ES 1.12 and P = 0.002, ES 1.11, respectively) in the SLE T group when compared with the NT group. Moreover, the HR response in SLE patients after training achieved parameters comparable to the C group, as evidenced by the analysis of variance and by the Z score analysis (P > 0.05, T versus C). Systemic Lupus Erythematosus Disease Activity Index scores remained stable throughout the study. Conclusion. A 3-month exercise training program was safe and capable of reducing the chronotropic incompetence and the delayed Delta HRR observed in physically inactive SLE patients.

Tricuspid Valve Injury After Heart Transplantation Due to Endomyocardial Biopsy: An Analysis of 3550 Biopsies

Introduction. Tricuspid regurgitation (TR) is the most commonly valvular dysfunction found after heart transplantation (HTx). It may be related to endomyocardial biopsy (EMB) performed for allograft rejection surveillance. Objective. This investigation evaluated the presence of tricuspid valve tissue fragments obtained during routine EMB performed after HTx and its possible effect on short-term and long-term hemodynamic status. Method. This single-center review included prospectively collected and retrospectively analyzed data. From 1985 to 2010, 417 patients underwent 3550 EMB after HTx. All myocardial specimens were reviewed to identify the presence of tricuspid valve tissue by 2 observers initially and in doubtful cases by a third observer. The echocardiographic and hemodynamic parameters were only considered for valvular functional damage analysis in cases of tricuspid tissue inadvertently removed during EMB. Results. The 417 HTx patients to 3550 EMB, including 17,550 myocardial specimens. Tricuspid valve tissue was observed in 12 (2.9%) patients corresponding to 0.07% of the removed fragments. The echocardiographic and hemodynamic parameters of these patients before versus after the biopsy showed increased TR in 2 cases (2/12; 16.7%) quantified as moderate without progression in the long term. Only the right atrial pressure showed a significant increase (P = .0420) after tricuspid injury; however, the worsening of the functional class was not significant enough in any of the subjects. Thus, surgical intervention was not required. Conclusions. Histological evidence of chordal tissue in EMB specimens is a real-world problem of relatively low frequency. Traumatic tricuspid valve injury due to EMB rarely leads to severe valvular regurgitation; only a minority of patients develop significant clinical symptoms. Hemodynamic and echocardiographic alterations are also less often observed in most patients.

Risk Factor Analysis of Late Survival After Heart Transplantation According to Donor Profile: A Multi-Institutional Retrospective Study of 512 Transplants

Introduction. Patients with terminal heart failure have increased more than the available organs leading to a high mortality rate on the waiting list. Use of Marginal and expanded criteria donors has increased due to the heart shortage. Objective. We analyzed all heart transplantations (HTx) in Sao Paulo state over 8 years for donor profile and recipient risk factors. Method. This multi-institutional review collected HTx data from all institutions in the state of Sao Paulo, Brazil. From 2002 to 2008 (6 years), only 512 (28.8%) of 1777 available heart donors were accepted for transplantation. All medical records were analyzed retrospectively; none of the used donors was excluded, even those considered to be nonstandard. Results. The hospital mortality rate was 27.9% (n = 143) and the average follow-up time was 29.4 +/- 28.4 months. The survival rate was 55.5% (n = 285) at 6 years after HTx. Univariate analysis showed the following factors to impact survival: age (P = .0004), arterial hypertension (P = .4620), norepinephrine (P = .0450), cardiac arrest (P = .8500), diabetes mellitus (P = .5120), infection (P = .1470), CKMB (creatine kinase MB) (P = .8694), creatinine (P = .7225), and Na+ (P = .3273). On multivariate analysis, only age showed significance; logistic regression showed a significant cut-off at 40 years: organs from donors older than 40 years showed a lower late survival rates (P = .0032). Conclusions. Donor age older than 40 years represents an important risk factor for survival after HTx. Neither donor gender nor norepinephrine use negatively affected early survival.

Comparative Analysis of the Complications of 5347 Endomyocardial Biopsies Applied to Patients After Heart Transplantation and With Cardiomyopathies: A Single-center Study

Introduction. Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. Objective. The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between FIT versus no-HT patients. Method. We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. Results. The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid Injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). Conclusions. EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.

Lipid transfers to HDL are predictors of precocious clinical coronary heart disease

Background: High-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function. Methods: Thirty normocholesterolemic CAD patients aged <50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol. cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL. Results: LDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8 +/- 1.2%vs 7.0 +/- 33%,p<0.0001) and triglycerides (3.7 +/- 1.7%vs 4.9 +/- 1.9%, p = 0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5 +/- 1.9%vs 4.8 +/- 1.8%, p = 0.0008); phospholipid transfer was equal (17.8 +/- 3.5% vs19.5 +/- 3.9%). Conclusion: Alterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies. (C) 2011 Published by Elsevier B.V.

Strength training with and without a vibration platform is capable to modulate heart rate variability?

The current research compared resting heart rate variability (VFC) before and after 10 weeks of strength training in groups that used and did not use a vibration platform. Seventeen healthy men were divided into conventional strength training (TF) or strength training using a vibration platform with a frequency of 30 Hz (TF+V30) training groups. One repetition maximum load (1-RM) on half squat exercise and VFC measurements were determined pre- and post-training program. Both groups had improved 1-RM load after the program (15.1% in TF group and 16.4% in TF+V30 group), although this increase was changed in the same extent for the two groups and there was no difference in 1-RM load between groups pre- and post-training program. No significant difference was observed in resting VFC measurements between groups pre and post-training program, however the magnitude of the effect size was moderated (ES = 0.50-0.80) for some variables (R-R interval, standard deviation of all R-R interval - SDNN, RMSSD, log-transformed of low frequency - InLF, and log-transformed of high frequency - InHF) in TF+V30 group. It was concluded that 10 weeks of strength training program with or without the vibration platform provided similar increase in 1-RM load in both groups, and although some evidences in this study indicate that vibration can increase vagal activity analyzed by ES, in neither groups the strength training was able to change VFC significantly.

Effects of neuromuscular electrostimulation in patients with heart failure admitted to ward

Background: Neuromuscular electrostimulation has become a promising issue in cardiovascular rehabilitation. However there are few articles published in the literature regarding neuromuscular electrostimulation in patients with heart failure during hospital stay. Methods: This is a randomized controlled pilot trial that aimed to investigate the effect of neuromuscular electrostimulation in the walked distance by the six-minute walking test in 30 patients admitted to ward for heart failure treatment in a tertiary cardiology hospital. Patients in the intervention group performed a conventional rehabilitation and neuromuscular electrostimulation. Patients underwent 60 minutes of electrostimulation (wave frequency was 20 Hz, pulse duration of 20 us) two times a day for consecutive days until hospital discharge. Results: The walked distance in the six-minute walking test improved 75% in the electrostimulation group (from 379.7 +/- 43.5 to 372.9 +/- 46.9 meters to controls and from 372.9 +/- 62.4 to 500 +/- 68 meters to electrostimulation, p<0.001). On the other hand, the walked distance in the control group did not change. Conclusion: The neuromuscular electrostimulation group showed greater improvement in the walked distance in the six-minute walking test in patients admitted to ward for compensation of heart failure.