Left atrial (LA) strain (epsilon) and epsilon rate (SR) analysis by two-dimensional speckle tracking can represent a new tool to evaluate LA function. To assess its potential value, the authors ...addressed whether LA epsilon and SR measured in normal subjects correlates with other Doppler echocardiographic parameters that evaluate LA function and left ventricular function.
Sixty-four healthy subjects were studied. LA epsilon and SR were calculated with the reference point set at the P wave, which enabled the recognition of peak negative epsilon (epsilon(neg peak)), peak positive epsilon (epsilon(pos peak)), and the sum of those values, total LA epsilon (epsilon(tot)), corresponding to LA contractile, conduit, and reservoir function, respectively. Similarly, peak negative SR (LA SR(late neg peak)) during LA contraction, peak positive SR (LA SR(pos peak)) at the beginning of LV systole, and peak negative SR (LA SR(early neg peak)) at the beginning of LV diastole were identified.
Global LA epsilon(pos peak), epsilon(neg peak), and epsilon(tot) were 23.2 +/- 6.7%, -14.6 +/- 3.5%, and 37.9 +/- 7.6%, respectively. Global LA SR(pos peak), SR(early neg peak) , and SR(late neg peak) were 2.0 +/- 0.6 s(-1), -2.0 +/- 0.6 s(-1), and -2.3 +/- 0.5 s(-1), respectively. The above-described variables derived from analysis of global LA epsilon and LA SR correlated significantly with Doppler echocardiographic indexes that evaluated the same phase of the cardiac cycle or the same component of the LA function, including indexes derived from mitral inflow, pulmonary vein velocities, tissue Doppler, and LA volumes. Global LA epsilon(pos peak), LA epsilon(tot), and LA SR(early neg peak) also correlated significantly with age or body mass index. Global LA SR(late neg peak) also correlated significantly with age.
LA epsilon analysis is a new tool that can be used to evaluate LA function. Further studies are warranted to determine the utility of LA epsilon in disease states.
Although protein S-nitrosylation is increasingly recognized as mediating nitric oxide (NO) signaling, roles for protein denitrosylation in physiology remain unknown. Here, we show that ...S-nitrosoglutathione reductase (GSNOR), an enzyme that governs levels of S-nitrosylation by promoting protein denitrosylation, regulates both peripheral vascular tone and β-adrenergic agonist-stimulated cardiac contractility, previously ascribed exclusively to NO/cGMP. GSNOR-deficient mice exhibited reduced peripheral vascular tone and depressed β-adrenergic inotropic responses that were associated with impaired β-agonist–induced denitrosylation of cardiac ryanodine receptor 2 (RyR2), resulting in calcium leak. These results indicate that systemic hemodynamic responses (vascular tone and cardiac contractility), both under basal conditions and after adrenergic activation, are regulated through concerted actions of NO synthase/GSNOR and that aberrant denitrosylation impairs cardiovascular function. Our findings support the notion that dynamic S-nitrosylation/denitrosylation reactions are essential in cardiovascular regulation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The anti-inflammatory cytokine transforming growth factor beta (TGF-β) plays an important role in Chagas disease (CD), a potentially life-threatening illness caused by
. In this review we revisited ...clinical studies in CD patients combined with
and
experiments, presenting three main sections: an overview of epidemiological, economic, and clinical aspects of CD and the need for new biomarkers and treatment; a brief panorama of TGF-β roles and its intracellular signaling pathways, and an update of what is known about TGF-β and Chagas disease. In
assays, TGF-β increases during
infection and modulates heart cells invasion by the parasite fostering its intracellular parasite cycle. TGF-β modulates host immune response and inflammation, increases heart fibrosis, stimulates remodeling, and slows heart conduction
gap junction modulation. TGF-β signaling inhibitors reverts these effects opening a promising therapeutic approach in pre-clinical studies. CD patients with higher TGF-β1 serum level show a worse clinical outcome, implicating a predictive value of serum TGF-β as a surrogate biomarker of clinical relevance. Moreover, pre-clinical studies in chronic
infected mice proved that inhibition of TGF-β pathway improved several cardiac electric parameters, reversed the loss of connexin-43 enriched intercellular plaques, reduced fibrosis of the cardiac tissue, restored GATA-6 and Tbox-5 transcription, supporting cardiac recovery. Finally, TGF-β polymorphisms indicate that CD immunogenetics is at the base of this phenomenon. We searched in a Brazilian population five single-nucleotide polymorphisms (-800 G>A rs1800468, -509 C>T rs1800469, +10 T>C rs1800470, +25 G>C rs1800471, and +263 C>T rs1800472), showing that CD patients frequently express the TGF-β1 gene genotypes CT and TT at position -509, as compared to noninfected persons; similar results were observed with genotypes TC and CC at codon +10 of the TGF-β1 gene, leading to the conclusion that 509 C>T and +10 T>C TGF-β1 polymorphisms are associated with Chagas disease susceptibility. Studies in genetically different populations susceptible to CD will help to gather new insights and encourage the use of TGF-β as a CD biomarker.
Chagas heart disease has a high socioeconomic burden, and any strategy to detect early myocardial damage is welcome. Speckle-tracking echocardiography assesses global and segmental left ventricular ...(LV) systolic function, yielding values of two-dimensional strain (ε). The aim of this study was to determine if patients with chronic Chagas disease and normal LV ejection fractions present abnormalities in global and segmental LV ε.
In this prospective study, patients with Chagas disease with no evidence of cardiac involvement (group I; n = 83) or at stage A of the cardiac form (i.e., with changes limited to the electrocardiogram) (group A; n = 42) and 43 control subjects (group C) underwent evaluation of global and segmental LV ε by speckle-tracking echocardiography. A subset of randomly selected patients in group A underwent cardiac magnetic resonance imaging and repeated echocardiography 3.5 ± 0.8 years after the first evaluation.
Mean age, chamber dimensions, and LV ejection fraction were similar among the groups. Global longitudinal (group C, -19 ± 2%; group I, -19 ± 2%; group A, -19 ± 2%), circumferential (group C, -19 ± 3%; group I, -20 ± 3%; group A, -19 ± 3%), and radial (group C, 46 ± 10%; group I, 45 ± 13%; group A, 42 ± 14%) LV ε were similar among the groups. Segmental longitudinal, circumferential, and radial LV ε were similar across the studied groups. Seven of 14 patients had areas of fibrosis on cardiac magnetic resonance imaging. Patients with fibrosis had lower global longitudinal (-15 ± 2% vs -18 ± 2%, P = .004), circumferential (-14 ± 2% vs -19 ± 2%, P = .002), and radial LV ε (36 ± 13% vs 54 ± 12%, P = .02) than those without cardiac fibrosis despite similar LV ejection fractions. Patients with fibrosis had lower radial LV ε in the basal inferoseptal wall than patients without cardiac fibrosis (27 ± 17% vs 60 ± 15%, P = .04).
Patients with chronic Chagas disease and normal global and segmental LV systolic function on two-dimensional echocardiography had global and segmental LV ε similar to that of control subjects. However, those in the early stages of the cardiac form and cardiac fibrosis had lower global longitudinal, circumferential, and radial LV ε.
A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD).
To study the association of clinical, ...electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD.
This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant.
Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 95% confidence interval (CI) 0.30-0.93; p = 0.03}, right bundle branch block OR 1.78 (95% CI 1.09-2.89); p = 0.02, and history of trypanocidal treatment OR 0.13 (95% CI 0.04-0.38); p = 0.0002. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR.
Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.
Chagas disease (CD) is still an important public health issue in Latin America. This study aims to analyse the association between socio-epidemiological factors and comorbidities with clinical ...manifestations of CD.
We performed a cross-sectional study of 985 adult patients (65±11 y; 59.5% women) with CD. Data collection was based on questionnaires and medical records review. CD clinical forms (indeterminate, digestive, cardiac and cardiodigestive) and the stages of the cardiac form were classified according to the II Brazilian Consensus on CD. Statistical analyses were based on univariate and multivariate logistic regression.
Older age and Brazilian birth state (Minas Gerais and Bahia) were associated with a greater likelihood of the cardiac form of CD. A greater likelihood of the digestive form was seen in men and those of older age. Patients with arterial hypertension and diabetes were less likely to have the digestive form. Men had a greater likelihood of having a more severe cardiac presentation. Those from Minas Gerais and Bahia states had a greater likelihood of having stage B1 or B2.
The results reinforce the aging of the CD population living in urban areas in Brazil, the high prevalence of comorbidities and that epidemiology, sex and the presence of comorbidities may be related to the clinical form of CD.
For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies ...conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by
infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions "
?" and "
?", we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-β as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-β pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.
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Abstract Introduction Infective endocarditis (IE) is still associated with high mortality, and antibiotic prophylaxis strategies are under intense debate. We evaluated the incidence of bacteremia ...after root canal preparation in teeth with necrotic pulps and apical periodontitis. Methods Blood samples were taken before and 5 and 30 minutes after endodontic treatment in teeth with apical periodontitis from individuals at high ( n = 21) or no risk ( n = 11) for IE. The former received prophylactic antibiotic therapy. Bacteriologic samples were taken from root canals before chemomechanical preparation to confirm pulp infection. Samples were subjected to aerobic and anaerobic culture and quantitative real-time polymerase chain reaction (qPCR), the latter to determine the total bacterial and streptococcal levels. Results Culture revealed no bacteremia in all individuals. Analysis by qPCR showed that bacterial DNA occurred in all root canal samples. qPCR showed a similar incidence of bacteremia between patients who received or did not receive prophylactic antibiotic therapy ( P > .05). In blood samples taken 5 minutes after endodontic procedures, bacteria were detected in 2 of 11 (18%) individuals not taking antibiotics and in 4 of 21 (19%) patients under prophylaxis. After 30 minutes, the incidence of bacteremia decreased to 2 of 21 (10%) in patients taking antibiotics and was undetectable in patients at no risk of IE. The incidence of bacteremia by streptococci was identical as that for total bacteria. Conclusions No detectable bacteremia was evident by culture after treatment of infected root canals. Molecular analysis revealed bacterial DNA and streptococci in blood from some patients without a significant difference between individuals receiving or not receiving antibiotic prophylaxis.
Although impaired left ventricular (LV) filling in constrictive pericarditis (CP) is attributable to external constraints by a tethered pericardium, impaired left atrial (LA) function can further ...impair LV filling. Previous studies focused on the impact of a tethered pericardium on LV diastolic behavior, but its impact on LA function has been largely overlooked. The objectives of this study were to evaluate LA mechanics in CP and to assess the impact of pericardiectomy on LA mechanics.
A total of 52 patients with CP (mean age, 57 ± 12 years) and 19 control subjects were studied retrospectively. All patients with CP underwent echocardiography before (median, 12 days; interquartile range, 5-34 days) and after pericardiectomy (median, 20 days; interquartile range, 5-64 days). Global LA longitudinal strain (ε) was calculated, which included peak negative ε (εnegative), peak positive ε (εpositive), and the sum of those values, total LA ε (εtotal), using speckle-tracking echocardiography with Velocity Vector Imaging. The regional difference of LA ε between the septal and lateral walls was assessed before and after the procedure.
Patients with CP showed depressed global LA εnegative, LA εtotal, and LA εpositive compared with controls. LA contractile (global LA εnegative) and reservoir functions (global LA εtotal) showed significant increases after pericardiectomy. Regional analysis revealed that the improvement in LA function after surgery was more apparent in lateral segments, while the regional function of septal walls was depressed after surgery.
Patients with CP have impaired LA mechanics, presumably because of the constrictive tethering process involving the left atrium. Speckle-tracking echocardiography showed consistent results of changes in LA mechanics with conventional echocardiographic parameters early after the procedure. Regional ε analysis aided in recognition of the impact of constrictive tethering and pericardiectomy on LA function.