Evaluation of systemic endothelial-dependent and endothelial-independent microvascular reactivity in metabolically healthy obesity: An observational study.

BACKGROUND: Metabolically healthy obesity (MHO), a phenotype of obesity considered to be of lower cardiovascular risk, is still a controversial concept. This study aimed to investigate the presence of subclinical systemic microvascular dysfunction in individuals with MHO. METHODS: This was a cross-sectional study in which 112 volunteers were allocated into three groups: metabolically healthy normal weight (MHNW), MHO, or metabolically unhealthy obesity (MUO). Obesity was defined as a body mass index (BMI) ≥ 30 kg/m2. MHO was defined as the absence of any component of metabolic syndrome, except waist circumference. Microvascular reactivity was evaluated using cutaneous laser speckle contrast imaging. RESULTS: Mean age was 33.2 ± 7.66 years. The median BMI in the MHNW, MHO and MUO groups was 23.6, 32.8, and 35.8 kg/m2, respectively. Baseline microvascular conductance values were lower in the MUO group (0.25 ± 0.08 APU/mmHg) than in MHO (0.30 ± 0.10 APU/mmHg) and MHNW groups (0.33 ± 0.12 APU/mmHg) (P = 0.0008). There were no significant differences regarding endothelial-dependent (acetylcholine stimulation or postocclusive reactive hyperemia) or endothelial-independent (sodium nitroprusside stimulation) microvascular reactivity among the groups. CONCLUSIONS: Individuals with MUO had lower baseline systemic microvascular flow than those with MHNW or MHO, but endothelium-dependent or endothelium-independent microvascular reactivity were not changed in any of the groups. The relatively young age of the study population, the low frequency of class III obesity, or the strict definition of MHO (absence of any metabolic syndrome criteria) might account for the lack of difference of microvascular reactivity among MHNW, MHO or MUO.

Effects of Whey Protein Isolate on Body Composition, Muscle Mass, and Strength of Chronic Heart Failure Patients: A Randomized Clinical Trial.

Heart failure (HF) is associated with a reduction of skeletal muscle mass. Whey protein isolate (WPI) has been beneficial in increasing muscle mass and strength, in addition to improving body composition. The goal of this research was to evaluate the effect of WPI on the body composition, muscle mass, and strength of chronic HF patients. For this purpose, twenty-five patients of both genders with predominantly NYHA I functional class and a median age of 65.5 (60.5-71.0) years were used to conduct a randomized, single-blind, placebo-controlled clinical trial and received 30 g per day of WPI for 12 weeks. Anthropometric measurements, body composition analysis, and biochemical exams were performed at the beginning and end of the study. An increase in skeletal muscle mass was observed in the intervention group after 12 weeks. A reduction in waist circumference, body fat percentage, and an increase in skeletal muscle index was observed when compared to the placebo group. No significant effect on muscle strength was observed after 12 weeks of intervention. These data demonstrate that WPI consumption contributed to the increase of skeletal muscle mass, strength, and reduction of body fat in HF patients.

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19).

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Evaluation of DNA damage induced by ionizing radiation from myocardial perfusion imaging: a pilot study.

BACKGROUND: As patient exposure to ionizing radiation raises concern about malignancy risks, this study evaluated the effect of ionizing radiation on patients undergoing myocardial perfusion imaging (MPI) using the comet assay, a method for detection of DNA damage. METHODS: Patients without cancer, acute or autoimmune diseases, recent surgery or trauma, were studied. Gated single-photon myocardial perfusion imaging was performed with Tc-99m sestamibi. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. Single-cell gel electrophoresis (comet assay) was performed with blood lymphocytes to detect strand breaks, which determine a "comet tail" of variable size, visually scored by 3 observers in a fluorescence microscope after staining (0: no damage, no tail; 1: small damage; 2: large damage; 3: full damage). A damage index was calculated as a weighted average of the cell scores. RESULTS: Among the 29 individuals included in the analysis, age was 65.3 ± 9.9 years and 18 (62.1%) were male. The injected radiotracer dose was 880.6 ± 229.4 MBq. Most cells (approximately 70%) remained without DNA fragmentation (class 0) after tracer injection. There were nonsignificant increases of classes 1 and 2 of damage. Class 3 was the least frequent both before and after radiotracer injection, but displayed a significant, 44% increase after injection. CONCLUSION: While lymphocytes mostly remained in class 0, an increase in class 3 DNA damage was detected. This may suggest that, despite a probable lack of biologically relevant DNA damage, there is still a need for tracer dose reductions in MPI.

Feasibility and Safety of Ipsilateral Ulnar Access in Cases of Impossibility or Failure of Radial Access for Coronary Angiography or Percutaneous Coronary Intervention.

OBJECTIVES: To evaluate the feasibility and safety of using the ulnar access in coronary angiography and percutaneous coronary intervention, in the failure or contraindication of ipsilateral radial access. METHODS: We prospectively evaluated, in a quaternary hospital, patients undergoing coronary angiography or percutaneous coronary intervention by transulnar approach, in case of failure or contraindication to the ipsilateral radial access. RESULTS: Between August 2018 and March 2020, of the 5,916 invasive coronary procedures performed, 2.2% were by transulnar approach. In the 130 patients evaluated, the indication for use of the transulnar approach was predominantly the low-amplitude or difficult to palpate radial pulse when compared to the ulnar artery (39.2%), followed by occlusion of the ipsilateral radial artery (33.1%). Complications of using the transulnar approach were superficial hematoma or low-degree muscle infiltration with extension ≤10 cm, in 6 patients (4.5%), and in 5 cases (3.8%) hematoma >10 cm. There was a case of transient ischemia of the hand due to forearm hematoma, treated conservatively. No cases of arterial thrombosis, pseudoaneurysm, arteriovenous fistula, symptomatic ulnar artery occlusion or ulnar nerve injury were observed after 30-day follow-up. CONCLUSION: The use of ipsilateral transulnar access is a feasible and safe alternative in cases where radial access would be impossible. This access site is associated with a low incidence of complications, which, when present, are most commonly associated with the occurance of spasm after the attempted radial puncture.

COVID-19 in patients with cardiac disease: Impact and variables associated with mortality in a cardiology center in Brazil.

BACKGROUND: Cardiovascular disease is associated with severe COVID-19. Our aim was to describe clinical and laboratory features (including electrocardiographic and echocardiographic ones) and outcomes of patients with cardiac disease hospitalized with COVID-19. METHODS: This is an observational retrospective study of consecutive adult patients admitted, between March and September of 2020, with confirmed SARSCoV-2 infection. Data were collected as per the ISARIC case report form and complemented with variables related to heart disease. RESULTS: One hundred twenty-one patients were included. Mean age was 60 SD 15.2 years and 80/121(66.1%) were male. Two-thirds of the patients (80/121, 66.1%) had COVID-19 at the time of hospital admission and COVID-19 was the reason for hospitalization in 42 (34.7%). Other reasons for hospital admission were acute coronary syndrome (26%) and decompensated heart failure (14.8%). Chronic cardiac diseases were found in 106/121 (87.6%), mostly coronary artery disease (62%) or valve disease (33.9%). A transthoracic echocardiogram was performed in 93/121(76.8%) and enlarged cardiac chambers were found in 71% (66/93); admission ECG was done in 93 cases (93/121, 76.8%), and 89.2% (83/93) were abnormal. Hospital-acquisition of COVID-19 occurred in 20 (16.5%) of patients and their mortality was 50%. On bivariate analysis for mortality, BNP levels and troponin levels were NOT associated with mortality. On multivariate analysis, only C reactive protein levels and creatinine levels were significant. CONCLUSIONS: COVID-19 impacted the profile of hospital admissions in cardiac patients. BNP and troponin levels were not associated with mortality and may not be good prognostic discriminators in cardiac patients.

Generative adversarial networks for generating synthetic features for Wi-Fi signal quality.

Wireless networks are among the fundamental technologies used to connect people. Considering the constant advancements in the field, telecommunication operators must guarantee a high-quality service to keep their customer portfolio. To ensure this high-quality service, it is common to establish partnerships with specialized technology companies that deliver software services in order to monitor the networks and identify faults and respective solutions. A common barrier faced by these specialized companies is the lack of data to develop and test their products. This paper investigates the use of generative adversarial networks (GANs), which are state-of-the-art generative models, for generating synthetic telecommunication data related to Wi-Fi signal quality. We developed, trained, and compared two of the most used GAN architectures: the Vanilla GAN and the Wasserstein GAN (WGAN). Both models presented satisfactory results and were able to generate synthetic data similar to the real ones. In particular, the distribution of the synthetic data overlaps the distribution of the real data for all of the considered features. Moreover, the considered generative models can reproduce the same associations observed for the synthetic features. We chose the WGAN as the final model, but both models are suitable for addressing the problem at hand.

Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity.

The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic - obesity. Currently, several studies have documented the association between obesity and COVID-19 severity. The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are of diverse nature. Inflammation plays a central role in obesity. Metabolic alterations seen in obese patients are related to an inflammatory response, and several studies report elevated levels of circulating inflammatory cytokines in obese patients. Also, deregulated expression of adipokines, such as leptin and resistin, increase the expression of vascular adhesion molecule 1 and intercellular adhesion molecule 1 that contribute to increased vascular leukocyte adhesiveness and additional oxidative stress. Additionally, it is now recognized that the chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. In fact, vascular endothelial dysfunction may contribute to a unfavorable response of the endothelium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity may also provide a link to the increased cardiovascular events in these patients.

Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier, even before diabetes is diagnosed. CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers, which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control. The entire mechanism is still not elucidated, but several aspects of the pathophysiology of CAN have already been described, such as the production of advanced glycation end products, reactive oxygen species, nuclear factor kappa B, and pro-inflammatory cytokines. This microvascular complication is an important risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. It has also been suggested that, compared to other traditional cardiovascular risk factors, CAN progression may have a greater impact on cardiovascular disease development. However, CAN might be subclinical for several years, and a late diagnosis increases the mortality risk. The duration of the transition period from the subclinical to clinical stage remains unknown, but the progression of CAN is associated with a poor prognosis. Several tests can be used for CAN diagnosis, such as heart rate variability (HRV), cardiovascular autonomic reflex tests, and myocardial scintigraphy. Currently, it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV, which is a non-invasive test with a lower operating cost. Therefore, considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes, the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.

Global Left Ventricular Myocardial Work Efficiency and Long-Term Prognosis in Patients After ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Left ventricular (LV) global longitudinal strain has demonstrated incremental prognostic value over LV ejection fraction in patients with ST-segment-elevation myocardial infarction. However, LV global longitudinal strain does not take into consideration the effect of afterload. Novel speckle-tracking echocardiographic indices of myocardial work integrate blood pressure measurements (afterload) with LV global longitudinal strain. The present study aimed to investigate the prognostic value of global LV myocardial work efficiency (GLVMWE; reflecting LV performance) obtained from pressure-strain loops with echocardiography in patients with ST-segment-elevation myocardial infarction. METHODS: A total of 507 ST-segment-elevation myocardial infarction patients (mean age, 61±11 years; 76% men) were retrospectively analyzed. LV ejection fraction and GLVMWE were measured by transthoracic echocardiography within 48 hours of admission. GLVMWE was defined as the ratio of constructive work divided by the sum of constructive and wasted work in all LV segments and expressed as a percentage. Spline curve analysis was used to define the association between reduced GLVMWE and all-cause death. RESULTS: After a median follow-up of 80 months (interquartile range, 67-97 months), 40 (8%) patients died. Patients with reduced GLVMWE (<86%) showed higher cumulative rates of all-cause mortality (17.5% versus 4.7%; log-rank P<0.001) in comparison with patients with preserved GLVMWE (≥86%). Reduced GLVMWE (<86%) showed an independent association with all-cause mortality (hazard ratio, 3.167 [95% CI, 1.679-5.972]; P<0.001). CONCLUSIONS: Reduced GLVMWE (<86%) measured by transthoracic echocardiography within 48 hours of admission in ST-segment-elevation myocardial infarction patients is associated with worse long-term survival.

Systemic microvascular endothelial dysfunction is associated with left ventricular ejection fraction reduction in chronic Chagas disease patients.

OBJECTIVE: This study compares microvascular reactivity (MR) in chronic Chagas disease (CD) patients with healthy individuals, matched for sex and age. In addition, we evaluated the association between MR and left ventricular ejection fraction (LVEF) in patients. METHODS: Acetylcholine iontophoresis was performed on the forearm skin, using laser speckle contrast imaging, to evaluate endothelium-dependent vasodilation. Clinical data were obtained from medical records. RESULTS: Thirty-six patients were compared to 25 healthy individuals (controls). Vasodilation was higher in controls, when compared to patients (p < .0001). There was a significant association between LVEF, stratified into quartiles, and MR (p-value for linear trend = .002). In addition, there was no difference in MR between patients with normal LVEF and the control group. In patients, MR was independent of the presence of arterial hypertension or diabetes. CONCLUSIONS: We have shown for the first time that the reduction of MR is associated with a decrease of LVEF in a cohort of chronic CD patients. The results were not affected by comorbidities, such as hypertension or diabetes. The evaluation of systemic endothelial function may be useful to tailor therapeutic and preventive approaches, targeted at systolic left ventricular failure associated with chronic CD cardiomyopathy.

Automatic Search-and-Replace From Examples With Coevolutionary Genetic Programming.

We describe the design and implementation of a system for executing search-and-replace text processing tasks automatically, based only on examples of the desired behavior. The examples consist of pairs describing the original string and the desired modified string. Their construction, thus, does not require any specific technical skill. The system constructs a solution to the specified task that can be used unchanged on popular existing software for text processing. The solution consists of a search pattern coupled with a replacement expression: the former is a regular expression which describes both the strings to be replaced and their portions to be reused in the latter, which describes how to build the modified strings. Our proposed system is internally based on genetic programming and implements a form of cooperative coevolution in which two separate populations are evolved independently, one for search patterns and the other for replacement expressions. We assess our proposal on six tasks of realistic complexity obtaining very good results, both in terms of absolute quality of the solutions and with respect to the challenging baselines considered.

Systemic microvascular endothelial dysfunction and disease severity in COVID-19 patients: Evaluation by laser Doppler perfusion monitoring and cytokine/chemokine analysis.

BACKGROUND: Microvascular dysfunction, serum cytokines and chemokines may play important roles in pathophysiology of coronavirus disease 2019 (COVID-19), especially in severe cases. METHODS: Patients with COVID-19 underwent non-invasive evaluation of systemic endothelium-dependent microvascular reactivity - using laser Doppler perfusion monitoring in the skin of the forearm - coupled to local thermal hyperemia. Maximal microvascular vasodilatation (44 °C thermal plateau phase) was used as endpoint. A multiplex biometric immunoassay was used to assess a panel of 48 serum cytokines and chemokines. Severe COVID-19 (S-COVID) was defined according to WHO criteria, while all other cases of COVID-19 were considered mild to moderate (M-COVID). A group of healthy individuals who tested negative for SARS-CoV-2 served as a control group and was also evaluated with LDPM. RESULTS: Thirty-two patients with COVID-19 (25% S-COVID) and 14 controls were included. Basal microvascular flow was similar between M-COVID and controls (P = 0.69) but was higher in S-COVID than in controls (P = 0.005) and M-COVID patients (P = 0.01). The peak microvascular vasodilator response was markedly decreased in both patient groups (M-COVID, P = 0.001; S-COVID, P < 0.0001) compared to the healthy group. The percent increases in microvascular flow were markedly reduced in both patient groups (M-COVID, P < 0.0001; S-COVID, P < 0.0001) compared to controls. Patients with S-COVID had markedly higher concentrations of dissimilar proinflammatory cytokines and chemokines, compared to patients with M-COVID. CONCLUSIONS: In patients with COVID-19, especially with S-COVID, endothelium-dependent microvascular vasodilator responses are reduced, while serum cytokines and chemokines involved in the regulation of vascular function and inflammation are increased.

Systemic microvascular dysfunction in COVID-19.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while having lung injury as its most prominent feature, has been increasingly shown to affect endothelial cell function and the microvasculature. In this report, a woman with COVID-19, cardiac valve disease and spherocytosis was assessed with laser Doppler perfusion monitoring. Systemic microvascular reactivity was impaired during a worsening phase of COVID-19, but improved after clinical recovery; microcirculatory dysfunction paralleled systemic inflammation and pulmonary involvement. The assessment of systemic microcirculatory function may therefore provide insights on COVID-19 pathophysiology.

COVID-19 and Microvascular Disease: Pathophysiology of SARS-CoV-2 Infection With Focus on the Renin-Angiotensin System.

The recently described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people, with thousands of fatalities. It has prompted global efforts in research, with focus on the pathophysiology of coronavirus disease-19 (COVID-19), and a rapid surge of publications. COVID-19 has been associated with a myriad of clinical manifestations, including the lungs, heart, kidneys, central nervous system, gastrointestinal system, skin, and blood coagulation abnormalities. The endothelium plays a key role in organ dysfunction associated with severe infection, and current data suggest that it is also involved in SARS-CoV-2-induced sepsis. This critical review aimed to address a possible unifying mechanism underlying the diverse complications of COVID-19: microvascular dysfunction, with emphasis on the renin-angiotensin system. In addition, research perspectives are suggested in order to expand understanding of the pathophysiology of the infection.

Acute cardiac injury in patients with COVID-19.

INTRODUCTION: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. METHODS: A systematic review with a meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independent reviewers evaluated the selected manuscripts for the outcome "myocardial injury", defined by troponin elevation above the 99th percentile. The study heterogeneity and risk of bias were evaluated. RESULTS: Eight studies, with a total of 1,229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9%-27%). The heterogeneity among the studies was high (93%). CONCLUSIONS: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% according to current studies. Continuous research is needed to update these findings as the pandemic evolves and to define the implications of myocardial injury in the context of this infection.

Emerging concepts in metabolically healthy obesity.

Obesity is a major risk factor for noncommunicable diseases that is responsible for more than 70% of early deaths in the world. In the 1980's decade, some studies started to describe a "benign" obesity phenotype, named "metabolically healthy obesity" (MHO), which represents obesity without comorbidities such as hypertension, cardiovascular diseases, insulin resistance, diabetes, dyslipidemia or metabolic syndrome. However, it is still unclear if this "benign" obesity phenotype is really favorable or just a transition status to unhealthy obesity and if these subjects presented subclinical levels of cardiovascular risk that are not commonly detected. To further elucidate these issues, the investigation of pathophysiological mechanisms that can increase cardiovascular risk in MHO individuals, such as hormones and cytokines, may offer some responses. In parallel, the evaluation of subclinical cardiovascular derangement, using the systemic microcirculation as a proxy, may be an alternative to anticipate overt cardiovascular disease. Overall, further studies are needed to better understand the pathophysiology of MHO as well as to identify high-risk individuals who deserve more intensive management.

Importance of the evaluation of systemic microvascular flow and reactivity in critically ill patients with coronavirus disease 2019 - COVID-19.

Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have, in fact, emerged as risk factors for a complicated evolution of COVID-19. Older age, cardiovascular disease including hypertension, diabetes and pulmonary disease, have been associated with more severe presentations and/or adverse prognosis. In this letter to the editor, we propose that the link between cardiovascular and metabolic diseases and the higher incidence and worse prognosis of COVID-19 patients is the (micro) vascular endothelium.