Multimodality imaging evaluation of Chagas disease: an expert consensus of Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI).

Aims: To develop a document by Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI) to review and summarize the most recent evidences about the non-invasive assessment of patients with Chagas disease, with the intent to set up a framework for standardized cardiovascular imaging to assess cardiovascular morphologic and functional disturbances, as well as to guide the subsequent process of clinical decision-making. Methods and results: Chagas disease remains one of the most prevalent infectious diseases in Latin America, and has become a health problem in non-endemic countries. Dilated cardiomyopathy is the most severe manifestation of Chagas disease, which causes substantial disability and early mortality in the socially most productive population leading to a significant economical burden. Prompt and correct diagnosis of Chagas disease requires specialized clinical expertise to recognize the unique features of this disease. The appropriate and efficient use of cardiac imaging is pivotal for diagnosing the cardiac involvement in Chagas disease, to stage the disease, assess patients' prognosis and address management. Echocardiography is the most common imaging modality used to assess, and follow-up patients with Chagas disease. The presence of echocardiographic abnormalities is of utmost importance, since it allows to stage patients according to disease progression. In early stages of cardiac involvement, echocardiography may demonstrate segmental left ventricuar wall motion abnormalities, mainly in the basal segments of inferior, inferolateral walls, and the apex, which cannot be attributed to obstructive coronary artery arteries. The prevalence of segmental wall motion abnormalities varies according to the stage of the disease, reaching about 50% in patients with left ventricular dilatation and dysfunction. Speckle tracking echocardiography allows a more precise and quantitative measurement of the regional myocardial function. Since segmental wall motion abnormalities are frequent in Chagas disease, speckle tracking echocardiography may have an important clinical application in these patients, particularly in the indeterminate forms when abnormalities are more subtle. Speckle tracking echocardiography can also quantify the heterogeneity of systolic contraction, which is associated with the risk of arrhythmic events. Three-dimensional (3D) echocardiography is superior to conventional two-dimensional (2D) echocardiography for assessing more accurately the left ventricular apex and thus to detect apical aneurysms and thrombus in patients in whom ventricular foreshortening is suspected by 2D echocardiography. In addition, 3D echocardiography is more accurate than 2D Simpson s biplane rule for assessing left ventricular volumes and function in patients with significant wall motion abnormalities, including aneurysms with distorted ventricular geometry. Contrast echocardiography has the advantage to enhancement of left ventricular endocardial border, allowing for more accurate detection of ventricular aneurysms and thrombus in Chagas disease. Diastolic dysfunction is an important hallmark of Chagas disease even in its early phases. In general, left ventricular diastolic and systolic dysfunction coexist and isolated diastolic dysfunction is uncommon but may be present in patients with the indeterminate form. Right ventricular dysfunction may be detected early in the disease course, but in general, the clinical manifestations occur late at advanced stages of Chagas cardiomyopathy. Several echocardiographic parameters have been used to assess right ventricular function in Chagas disease, including qualitative evaluation, myocardial performance index, tissue Doppler imaging, tricuspid annular plane systolic excursion, and speckle tracking strain. Cardiac magnetic resonance (CMR) is useful to assess global and regional left ventricular function in patients with Chagas diseases. Myocardial fibrosis is a striking feature of Chagas cardiomyopathy and late gadolinium enhancement (LGE) is used to detect and quantify the extension of myocardial fibrosis. Myocardial fibrosis might have a role in risk stratification of patients with Chagas disease. Limited data are available regarding right ventricular function assessed by CMR in Chagas disease. Radionuclide ventriculography is used for global biventricular function assessment in patients with suspected or definite cardiac involvement in Chagas disease with suboptimal acoustic window and contraindication to CMR. Myocardial perfusion scintigraphy may improve risk stratification to define cardiac involvement in Chagas disease, especially in the patients with devices who cannot be submitted to CMR and in the clinical setting of Chagas patients whose main complaint is atypical chest pain. Detection of reversible ischemic defects predicts further deterioration of left ventricular systolic function and helps to avoid unnecessary cardiac catheterization and coronary angiography. Conclusion: Cardiac imaging is crucial to detect the cardiac involvement in patients with Chagas disease, stage the disease and stratify patient risk and address management. Unfortunately, most patients live in regions with limited access to imaging methods and point-of-care, simplified protocols, could improve the access of these remote populations to important information that could impact in the clinical management of the disease. Therefore, there are many fields for further research in cardiac imaging in Chagas disease. How to better provide an earlier diagnosis of cardiac involvement and improve patients risk stratification remains to be addressed using different images modalities.

[Carotid intimal-medial thickening and endothelial function in coronary artery disease]. / Espessamento médio-intimal da carótida e função endotelial na doença arterial coronariana.

OBJECTIVE: To investigate the correlation between the endothelial function and the carotid intimal-medial thickening (IMT) in a population of patients with coronary artery disease, as well as that between the endothelial function and carotid IMT with the severity of the coronary lesions. METHODS: Forty-three patients aged 60.5+/-9.2 years, (67.4% males) with coronary artery disease at the coronariography were studied. Endothelial function was assessed using the brachial artery reactivity test (BART), which measured the percentage of flow-mediated dilatation (%FMD). The carotid IMT was evaluated through vascular ultrasound. RESULTS: The mean %FDM was 4.7 +/- 3.6 and the mean carotid IMT was 1.08 +/- 0.23 mm. The carotid MIT and %FMD measurements showed a statistically significant correlation, with Spearmans coefficient of 0.315, p= 0.042, demonstrating that lower %FMD values corresponded to an increased carotid IMT (r = -0.315, p = 0.042). There was no correlation between %FMD or IMT and the severity of coronary lesions. CONCLUSIONS: The presence of a correlation between carotid IMT and %FMD demonstrates a concomitance of anatomical and functional vascular alterations in coronary artery disease, regardless of the severity of the atherosclerotic lesions.

Espessamento médio-intimal da carótida e função endotelial na doença arterial coronariana / Carotid intimal-medial thickening and endothelial function in coronary artery disease

OBJETIVO: Investigar uma correlação entre o teste de reatividade da artéria braquial (BART) e o espessamento médio-intimal (EMI) da carótida em uma população de pacientes com doença arterial coronariana, assim como avaliar uma correlação do BART e do EMI da carótida com a gravidade da doença arterial coronariana demonstrada através da coronariografia. MÉTODOS: Quarenta e dois pacientes (idade: 60,7 ± 9,2 anos, 66,7 por cento do sexo masculino) com doença arterial coronariana por coronariografia foram estudados. A função endotelial foi avaliada de modo não-invasivo através do BART, quando foi medido o porcentual de dilatação mediada pelo fluxo ( por centoDMF). O EMI de carótida foi avaliado por meio de ultra-som vascular. RESULTADOS: A média de por centoDMF foi de 4,7 ± 3,6 e a média de EMI de carótida foi de 1,08 ± 0,23 mm. As medidas do EMI de carótida e do por centoDMF apresentaram correlação estatisticamente significativa, com coeficiente de Spearman de -0,315, valor p = 0,042, demonstrando que valores menores de por centoDMF se correlacionaram a um maior EMI de carótida. Não houve correlação entre por centoDMF, EMI e a gravidade das lesões; CONCLUSÃO: A presença de uma correlação entre o por centoDMF e o EMI da carótida demonstra a concomitância de alterações vasculares funcionais e anatômicas na doença arterial coronariana, independentemente da gravidade das lesões ateroscleróticas.

Modulation of Na+-channels by neurotoxins produces different effects on [3H]ACh release with mobilization of distinct Ca2+-channels.

1. Voltage-gated Na+ channels are responsible for initiation and conduction of action potentials. The arrival of an action potential at nerve terminal increases intracellular Na+ and Ca2+ concentrations. Calcium entry into neurons through voltage-dependent calcium channels is associated with a variety of intracellular processes. Scorpion neurotoxins have been used as tools to investigate mechanisms involved in neurotransmitter release. Tityustoxin (TsTX) is an alpha-type toxin that delays Na+-channel inactivation. Toxin-gamma (TiTX-gamma) is a beta-type toxin that induces Na+-channel activation at resting potentials. 2. In the present work, we describe the effects of both toxins on [3H]acetylcholine ([3H]ACh) release from rat cerebrocortical synaptosomes, in the presence or absence of the calcium channels blockers: omega-conotoxin-GVIA (omega-CgTx), 1 microM; omega-agatoxin-IVA (omega-Aga), 30 nM; omega-conotoxin-MVIIC (omega-MVIIC), 1 microM; or verapamil, 1 microM. 3. TsTX evokes [3H]ACh release in a concentration-dependent manner with a gradual increase up to saturation at concentrations of 500 nM. However, release of ACh evoked by TiTX-gamma was not linear regarding the toxin concentration. The [3H]-ACh release evoked by TsTX or TiTX-gamma was partially inhibited by omega-CgTx or omega-Aga, and blocked with omega-MVIIC. Verapamil (1 microM) had no effect. Tetrodotoxin blocked [3H]ACh release evoked by both toxins. 4. These results show that different actions on Na+-channels produce different effects on [3H]ACh release with involvement of distinct presynaptic Ca2+-channels, which supports the idea that sodium channels may modulate neurotransmitter release.