Medição automática de valva mitral a partir de ecocardiograma utilizando processamento digital de imagens / Automatic measurement of the mitral valve based on echocardiography using digital image processing

Fundamento: A avaliação da área valvar mitral por meio da reconstrução multiplano na ecocardiografia tridimensional é restrita a softwares específicos e à experiência dos ecocardiografistas. Eles precisam selecionar manualmente o frame do vídeo que contenha a área de abertura máxima da valva mitral, dimensão fundamental para a identificação de estenose mitral. Objetivo: Automatizar o processo de determinação da área de abertura máxima da valva mitral, por meio da aplicação de Processamento Digital de Imagens (PDI) em exames de ecocardiograma, desenvolvendo um algoritmo aberto com leitura de vídeo no formato avi. Método: Este estudo piloto observacional transversal foi realizado com vinte e cinco exames diferentes de ecocardiograma, sendo quinze com abertura normal e dez com estenose mitral reumática. Todos os exames foram realizados e disponibilizados por dois especialistas, com autorização do Comitê de Ética em Pesquisa, que utilizaram dois modelos de aparelhos ecocardiográficos: Vivid E95 (GE Healthcare) e Epiq 7 (Philips), com sondas multiplanares transesofágicas. Todos os vídeos em formato avi foram submetidos ao PDI através da técnica de segmentação de imagens. Resultados: As medidas obtidas manualmente por ecocardiografistas experientes e os valores calculados pelo sistema desenvolvido foram comparados utilizando o diagrama de Bland-Altman. Observou-se maior concordância entre valores no intervalo de 0,4 a 2,7 cm². Conclusão: Foi possível determinar automaticamente a área de máxima abertura das valvas mitrais, tanto para os casos advindos da GE quanto da Philips, utilizando apenas um vídeo como dado de entrada. O algoritmo demonstrou economizar tempo nas medições quando comparado com a mensuração habitual. (AU)

Background: The evaluation of mitral valve area through multiplanar reconstruction in 3-dimensional echocardiography is restricted to specific software and to the experience of echocardiographers. They need to manually select the video frame that contains the maximum mitral valve opening area, as this dimension is fundamental to identification of mitral stenosis. Objective: To automate the process of determining the maximum mitral valve opening area, through the application of digital image processing (DIP) in echocardiography tests, developing an open algorithm with video reading in avi format. Method: This cross-sectional observational pilot study was conducted with 25 different echocardiography exams, 15 with normal aperture and 10 with rheumatic mitral stenosis. With the authorization of the Research Ethics Committee, all exams were performed and made available by 2 specialists who used 2 models of echocardiographic devices: Vivid E95 (GE Healthcare) and Epiq 7 (Philips), with multiplanar transesophageal probes. All videos in avi format were submitted to DIP using the image segmentation technique. Results: The measurements obtained manually by experienced echocardiographers and the values calculated by the developed system were compared using a Bland-Altman diagram. There was greater agreement between values in the range from 0.4 to 2.7 cm². Conclusion: It was possible to automatically determine the maximum mitral valve opening area, for cases from both GE and Philips, using only 1 video as input data. The algorithm has been demonstrated to save time on measurements when compared to the usual method. (AU)

What puts the heat on thermogenic fat: metabolism of fuel substrates.

Owing to its unique capacity to clear macronutrients from circulation and use them to produce heat, thermogenic fat is capable of regulating glucose, lipids, and branched-chain amino acids (BCAA) circulatory levels. At the same time, its activity yields a higher energy expenditure, thereby conferring protection against cardiometabolic diseases. Our knowledge on the mechanisms of uptake and intracellular metabolism of such energy substrates into thermogenic fat has meaningfully evolved in recent years. This has allowed us to better understand how the thermogenic machinery processes those molecules to utilize them as substrates for heating up the body. Here, we discuss recent advances in the molecular and cellular regulatory process that governs the uptake and metabolism of such substrates within thermogenic fat.

Combined training increases thermogenic fat activity in patients with overweight and type 2 diabetes.

BACKGROUND: Exercise is an important strategy in the management of diabetes. Experimental studies have shown that exercise acts, at least in part, by inducing the production of myokines that improve metabolic control and activate brown/beige adipose tissue depots. Combined training (CT) is recommended by the major diabetes guidelines due to its metabolic and cardiovascular benefits, however, its impact on brown/beige adipose tissue activities has never been tested in humans with overweight and type 2 diabetes (T2D). Here, we evaluated the effects of 16-week combined training (CT) program on brown adipose tissue activity; browning and autophagy markers, and serum pro-thermogenic/inflammatory inducers in patients with overweight and T2D. METHODS: Thirty-four patients with overweight and T2D were assigned to either a control group (CG) or a combined training group (CTG) in a randomized and controlled study. Functional/fitness parameters, anthropometry/body composition parameters, blood hormone/biochemical parameters, thermogenic/autophagic gene expression in subcutaneous adipose tissue were evaluated before and at the end of the intervention. In addition, cold-induced 18-Fluoroxyglucose Positron Emission Computed Tomography (18F-FDG PET/CT) was performed in the training group before and after the end of the intervention. RESULTS: CT increased cervical/supraclavicular brown adipose tissue (BAT) thermogenic activity (p = 0.03) as well as in perirenal adipose tissue (p = 0.02). In addition, CT increased the expression of genes related to thermogenic profile (TMEM26: + 95%, p = 0.04; and EPSTI1: + 26%, p = 0.03) and decreased autophagic genes (ULK1: -15%, p = 0.04; LC3: -5%, p = 0.02; and ATG4: -22%, p < 0.001) in subcutaneous adipose tissue. There were positive correlations between Δ% BAT activity with Δ% of post training energy expenditure cold exposure, HDL-c, IL4, adiponectin, irisin, meteorin-like, and TMEM26 and ZIC1 genes, besides negative correlations with LDL-c, total cholesterol and C-reactive protein. CONCLUSION: This is the first evidence of the beneficial actions of CT on adipose tissue thermogenic activity in humans, and it adds important support for the recommendation of CT as a strategy in the management of diabetes.

Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial.

BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.

Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity

BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden. (AU)

Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity.

BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.

Assessment of dapagliflozin effect on diabetic endothelial dysfunction of brachial artery (ADDENDA-BHS2 trial): rationale, design, and baseline characteristics of a randomized controlled trial.

BACKGROUND: Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. METHOD AND RESULTS: ADDENDA-BHS2 is a prospective, single-center, active-controlled, open, randomized trial. Ninety-eight participants (40-70 years old) with HbA1c 7-9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. CONCLUSION: The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations.Trial registration Clinical trial registration: NCT02919345 (September, 2016).

Reciprocal Multifaceted Interaction Between HDL (High-Density Lipoprotein) and Myocardial Infarction.

Despite decades of therapeutic advances, myocardial infarction remains a leading cause of death worldwide. Recent studies have identified HDLs (high-density lipoproteins) as a potential candidate for mitigating coronary ischemia/reperfusion injury via a broad spectrum of signaling pathways. HDL ligands, such as S1P (sphingosine-1-phosphate), Apo (apolipoprotein) A-I, clusterin, and miRNA, may influence the opening of the mitochondrial channel, insulin sensitivity, and production of vascular autacoids, such as NO, prostacyclin, and endothelin-1. In parallel, antioxidant activity and sequestration of oxidized molecules provided by HDL can attenuate the oxidative stress that triggers ischemia/reperfusion. Nevertheless, during myocardial infarction, oxidation and the capture of oxidized and proinflammatory molecules generate large phenotypic and functional changes in HDL, potentially limiting its beneficial properties. In this review, new findings from cellular and animal models, as well as from clinical studies, will be discussed to describe the cardioprotective benefits of HDL on myocardial infarction. Furthermore, mechanisms by which HDL modulates cardiac function and potential strategies to mitigate postmyocardial infarction risk damage by HDL will be detailed throughout the review.

Alterações simultâneas e múltiplas das funções da HDL seguem o excesso de peso / Simultaneous and multiple changes in HDL functions follow overweight

INTRODUÇÃO. A obesidade se associa a declínio na capacidade de efluxo de colesterol (CEC) mediada por HDL. Embora esse dado tenha apoiado a noção de que a disfunção do HDL contribui para a aterogênese em pacientes obesos, a perda funcional da HDL também pode envolver outros domínios funcionais e se estabelecer mesmo antes dos valores limiares para obesidade, ou seja, ainda em valores compatíveis com sobrepeso. MÉTODOS. Perfil lipídico, índice de massa corporal (IMC), medidas bioquímicas e espessura médio-intimal (cIMT) foram obtidos neste estudo transversal com 899 indivíduos assintomáticos. Funções de HDL e caracterização físico-química de HDL foram medidas em um subgrupo (n=101). RESULTADOS. Foi identificada interação do IMC sobre a associação entre HDL-C e cIMT (ß=-1,8; p<0,0001). Enquanto que, de forma geral, o HDL-C reduzido foi associado ao aumento da cIMT, os indivíduos com níveis elevados de HDL-C apresentaram associação atenuada entre o IMC e cIMT. Foi encontrada uma associação negativa entre CEC e cIMT (ß=-0,2; p<0,047) e entre atividade antioxidante de HDL e cIMT (ß=-0,2; p<0,038) mesmo após ajuste para idade, sexo, IMC, HDL-C e insulina no plasma. O IMC foi inversamente associado à inibição da agregação plaquetária mediada por HDL (r=-0,2, p<0,03) e CEC (r=-0,3, p<0,001), mas diretamente associada à atividade antioxidante (r=0,2, p<0,047). Uma variável composta de CEC e atividade antioxidante transformadas em z-score permaneceu aproximadamente constante à medida em que o tamanho de HDL se altera em função do excesso de peso. Valores crescentes dessa variável composta foram associados à cIMT (R2 polinomial=0,26, p<0,001), sugerindo que a alteração do tamanho da HDL pode representar uma adaptação biológica bem-sucedida ao excesso de peso. CONCLUSÃO. O aumento do IMC está associado à disfunção global da HDL, que contribui para aumentar a carga aterosclerótica. Nesse cenário, a alteração do tamanho da HDL não justifica o aumento do desenvolvimento da doença aterosclerótica. (AU)

Central role of obesity in endothelial cell dysfunction and cardiovascular risk.

Atherosclerosis is the leading cause of mortality in the contemporary world. The critical role of the endothelial cells (EC) in vascular homeostasis, the metabolic changes that take place when the cell is activated, and the elements involved in these processes have been widely explored over the past years. Obesity and its impact, promoting a rise in blood levels of free fatty acids (FAs) are often associated with atherosclerosis and cardiovascular mortality. However, the mechanisms that promote cardiovascular structural changes and adaptive changes in the ECs, particularly in the context of obesity, are little known. Here, we reviewed studies that assessed the metabolic adaptations of healthy and dysfunctional ECs during exposure to FAs, as well as the epidemiological perspectives of cardiovascular structural changes in obesity. Finally, we explored the role of new agents - sphingolipids, dietary unsaturated fatty acids and sodium-glucose cotransporter-2 inhibitors (iSGLT2) - in atherosclerosis and their relationship with obesity.

Central role of obesity in endothelial cell dysfunction and cardiovascular risk

SUMMARY Atherosclerosis is the leading cause of mortality in the contemporary world. The critical role of the endothelial cells (EC) in vascular homeostasis, the metabolic changes that take place when the cell is activated, and the elements involved in these processes have been widely explored over the past years. Obesity and its impact, promoting a rise in blood levels of free fatty acids (FAs) are often associated with atherosclerosis and cardiovascular mortality. However, the mechanisms that promote cardiovascular structural changes and adaptive changes in the ECs, particularly in the context of obesity, are little known. Here, we reviewed studies that assessed the metabolic adaptations of healthy and dysfunctional ECs during exposure to FAs, as well as the epidemiological perspectives of cardiovascular structural changes in obesity. Finally, we explored the role of new agents - sphingolipids, dietary unsaturated fatty acids and sodium-glucose cotransporter-2 inhibitors (iSGLT2) - in atherosclerosis and their relationship with obesity.

RESUMO A aterosclerose é a causa líder de mortalidade no mundo contemporâneo. O papel central da célula endotelial (EC) na homeostase vascular, as alterações metabólicas que ocorrem quando a célula se torna ativada e os elementos envolvidos nesses processos vêm sendo bastante explorados nos últimos anos. A obesidade e o seu impacto, promovendo uma elevação dos níveis sanguíneos de ácidos graxos (FAs) livres, é bastante associada à aterosclerose e à mortalidade cardiovascular. Entretanto, os mecanismos que promovem alterações estruturais cardiovasculares e alterações adaptativas nas ECs, particularmente no contexto da obesidade, são pouco conhecidos. Aqui, nós revisamos estudos que avaliaram as adaptações metabólicas das ECs normais e disfuncionais durante exposição a FAs, bem como as perspectivas epidemiológicas das alterações cardiovasculares estruturais na obesidade. Finalmente, exploramos o papel de novos atores — esfingolípides, ácidos graxos insaturados da dieta e inibidores do cotransportador de sódio-glucose 2 (iSGLT2) — na aterosclerose e sua relação com a obesidade.

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain-Adipocyte Axis.

The complexity of neural circuits that control food intake and energy balance in the hypothalamic nuclei explains some of the constraints involved in the prevention and treatment of obesity. Two major neuronal populations present in the arcuate nucleus control caloric intake and energy expenditure: one population co-expresses orexigenic agouti-related peptide (AgRP) and neuropeptide Y and the other expresses the anorexigenic anorectic neuropeptides proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). In addition to integrating signals from neurotransmitters and hormones, the hypothalamic systems that regulate energy homeostasis are affected by nutrients. Fat-rich diets, for instance, elicit hypothalamic inflammation (reactive activation and proliferation of microglia, a condition named gliosis). This process generates resistance to the anorexigenic hormones leptin and insulin, contributing to the genesis of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have increasingly been used to treat type 2 diabetes mellitus. One compound (liraglutide) was recently approved for the treatment of obesity. Although most studies suggest that GLP-1RAs promote weight loss mainly due to their inhibitory effect on food intake, other central effects that have been described for native GLP-1 and some GLP-1RAs in rodents and humans encourage future clinical trials to explore additional mechanisms that potentially underlie the beneficial effects observed with this drug class. In this article we review the most relevant data exploring the mechanisms involved in the effects of GLP-1RAs in the brain-adipocyte axis.

Spinal cord diffusion tensor imaging in patients with sensory neuronopathy.

INTRODUCTION: We investigated whether MR diffusion tensor imaging (DTI) analysis of the cervical spinal cord could aid the (differential) diagnosis of sensory neuronopathies, an underdiagnosed group of diseases of the peripheral nervous system. METHODS: We obtained spinal cord DTI and T2WI at 3 T from 28 patients, 14 diabetic subjects with sensory-motor distal polyneuropathy, and 20 healthy controls. We quantified DTI-based parameters and looked at the hyperintense T2W signal at the spinal cord posterior columns. Fractional anisotropy and mean diffusivity values at C2-C3 and C3-C4 levels were compared between groups. We also compared average fractional anisotropy (mean of values at C2-C3 and C3-C4 levels). A receiver operating characteristic (ROC) curve was used to determine diagnostic accuracy of average fractional anisotropy, and we compared its sensitivity against the hyperintense signal in segregating patients from the other subjects. RESULTS: Mean age and disease duration were 52 ± 10 and 11.4 ± 9.3 years in the patient group. Eighteen subjects had idiopathic disease and 6 dysimmune etiology. Fractional anisotropy at C3-C4 level and average fractional anisotropy were significantly different between patients and healthy controls (p < 0.001 and <0.001) and between patients and diabetic subjects (p = 0.019 and 0.027). Average fractional anisotropy presented an area under the curve of 0.838. Moreover, it had higher sensitivity than visual detection of the hyperintense signal (0.86 vs. 0.54), particularly for patients with short disease duration. CONCLUSION: DTI-based analysis enables in vivo detection of posterior column damage in sensory neuronopathy patients and is a useful diagnostic test for this condition. It also helps the differential diagnosis between sensory neuronopathy and distal polyneuropathies.

The Obese Brain--Effects of Bariatric Surgery on Energy Balance Neurocircuitry.

Obesity is a highly prevalent disease in the world and with a major impact on global health. While genetic components are also involved in its pathogenesis, in recent years, it has shown a critical role of the innate and adaptive immune cell response in many tissues triggered by excess of nutrients such as lipids and glucose. Free fatty acids and other nutrient-related signals induce damage such as insulin resistance in the peripheral tissues but also in the brain. Specifically in the hypothalamus, these metabolic signals can trigger significant changes in the control of energy balance. Recent studies have shown that saturated fat disrupts melanocortin signaling of hypothalamic neuronal subgroups pivotal to energy control. Bariatric surgery is a treatment option for obesity when other tools have failed, because it is more effective than pharmacotherapy concerning of weight loss itself and in improvement of obesity-related comorbidities. Here, we review the mechanisms by which Roux-en Y gastric bypass (RYGB) can change peripheral signals that modulate melanocortin circuits involved in the regulation of energy balance.