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.

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.

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.

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.

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.

Increased systemic endothelial-dependent microvascular reactivity after ingestion of a high-carbohydrate snack in young, healthy volunteers.

OBJECTIVE: This study evaluated the acute effect of a high-carbohydrate snack (HCS) on systemic microvascular function of healthy, young volunteers, using laser speckle contrast imaging (LSCI). METHODS: Cutaneous microvascular blood flow was assessed in the forearm with LSCI coupled to iontophoresis of acetylcholine, using increasing anodal currents, before and after (25 min) the ingestion of a HCS or water (control). Twenty volunteers (10 male) received a single HCS (70 g of carbohydrates) in the fasting state in the morning. RESULTS: The area under the curve (AUC) of acetylcholine-induced microvascular vasodilation increased from 17,847 ±â€¯4539 to 20,315 ±â€¯7168 arbitrary perfusion units/s (P = 0.03) after ingestion of a HCS, but was unchanged after the ingestion of water (P = 0.22). CONCLUSION: A single snack consisting on an acute oral load of carbohydrates induced a significant increase of endothelium-dependent microvascular vasodilation in healthy, young subjects.

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.

Microvascular Function and Endothelial Progenitor Cells in Patients with Severe Hypercholesterolemia and the Familial Hypercholesterolemia Phenotype.

OBJECTIVE: To evaluate endothelial progenitor cells (EPCs) and systemic microvascular function in patients with severe hypercholesterolemia, comparing patients with the definite familial hypercholesterolemia (FH) phenotype (DFH) or probable/possible FH phenotype (PFH). There is a large spectrum of atherosclerotic disease between these two clinical phenotypes of FH, and to acquire further knowledge of the pathophysiology of vascular disease in both is desirable. METHODS: Subjects with severe hypercholesterolemia, defined as low-density lipoprotein cholesterol (LDL-C) >190 mg/dL, were classified as DFH or PFH and underwent measurement of the number of EPCs by flow cytometry and evaluation of cutaneous microvascular reactivity using a laser speckle contrast-imaging system with iontophoresis of acethylcholine (ACh) or sodium nitroprusside. EPCs were defined as CD45- or CD45low, CD34+CD133+CD309+ cells. Categorical variables were compared using Fisher test and continuous variables with Student t test or Mann-Whitney test, and a value of p < 0.05 was considered statistically significant. RESULTS: Patients with DFH had higher LDL-C than those with PFH. There was no difference in the median number of EPCs between patients with DFH or PFH, but there was a significant reduction of endothelial-dependent, ACh-induced vasodilatation in the former. CONCLUSION: Patients with DFH have impaired microvascular endothelial-dependent vasodilatation compared to those with PFH, indicating more severe vascular disease in the former.

Acute cellular rejection and HLA mismatch in heart transplantation: insights from a developing country.

The notable evolution of heart transplant (HTX) has paralleled the capacity of diagnosing rejection and, consequently, initiating timely treatment. Acute cellular rejection, diagnosed by endomyocardial biopsy, is the most frequent in the first 6 months after HTX. HLA matching is not routinely performed in HTX due to the absence of consensus regarding its usefulness. However, the use of HLA typing might be underscored if it could predict an increased risk of rejection. Therefore, the aim of this study was to evaluate, at a public cardiology center in Brazil, the association between HLA mismatches and the incidence of acute cellular rejection in the first 6 months after HTX. Data were obtained from hospital records and from the National Transplant System. Overall, there was no association between the number of HLA mismatches and the frequency of acute cellular rejection, but there was a tendency toward a higher incidence of rejection with HLA-DR incompatibility.

Budget impact of applying appropriateness criteria for myocardial perfusion scintigraphy: The perspective of a developing country.

Myocardial perfusion imaging is widely used for the risk stratification of coronary artery disease. In view of its cost, besides radiation issues, judicious evaluation of the appropriateness of its indications is essential to prevent an unnecessary economic burden on the health system. We evaluated, at a tertiary-care, public Brazilian hospital, the appropriateness of myocardial perfusion scintigraphy indications, and estimated the budget impact of applying appropriateness criteria. An observational, cross-sectional study of 190 patients with suspected or known coronary artery disease referred for myocardial perfusion imaging was conducted. The appropriateness of myocardial perfusion imaging indications was evaluated with the Appropriate Use Criteria for Cardiac Radionuclide Imaging published in 2009. Budget impact analysis was performed with a deterministic model. The prevalence of appropriate requests was 78%; of inappropriate indications, 12%; and of uncertain indications, 10%. Budget impact analysis showed that the use of appropriateness criteria, applied to the population referred to myocardial perfusion scintigraphy within 1 year, could generate savings of $ 64,252.04 dollars. The 12% inappropriate requests for myocardial perfusion scintigraphy at a tertiary-care hospital suggest that a reappraisal of MPI indications is needed. Budget impact analysis estimated resource savings of 18.6% with the establishment of appropriateness criteria for MPI.

Reduced systemic microvascular density and reactivity in individuals with early onset coronary artery disease.

OBJECTIVE: This study sought to test whether patients with early-onset coronary artery disease (EOCAD, n=30) showed systemic microvascular rarefaction and endothelial dysfunction in comparison to age- and sex-matched healthy controls (CTL, n=30), as evaluated by skin video-capillaroscopy. METHODS: Functional capillary density (FCD) was defined as the number of spontaneously perfused capillaries per square millimeter of skin area and assessed by high-resolution intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using post-occlusive reactive hyperemia (PORH) after arm ischemia for 3min. RESULTS: The mean capillary density at rest was significantly reduced in patients with EOCAD compared to controls (CTL 95±20 and EOCAD 80±18capillaries/mm(2), P=0.0040). During PORH, capillary density was also markedly reduced in EOCAD patients (CTL 96±18 and EOCAD 71±20capillaries/mm(2), P<0.0001). Moreover, the capillary density in EOCAD patients was significantly reduced during PORH (EOCAD at rest 80±19 and EOCAD during PORH 71±20capillaries/mm(2), P=0.0073). CONCLUSIONS: Patients with EOCAD presented systemic capillary rarefaction and impaired microvascular endothelial function. Thus, the early detection of these microvascular alterations in young adults at an increased risk of coronary artery disease could be useful as a surrogate marker of subclinical atherosclerosis.

Association between Carotid Intima-media Thickness and Early-onset Coronary Artery Disease: Does the site of Sonographic Evaluation Matter?

BACKGROUND: Intima-media thickness (IMT) is frequently used for risk stratification (RS) due to the association with coronary artery disease (CAD). Nonetheless, the best carotid site to scan is uncertain, especially in the young. The aim of this study was to evaluate the diagnostic performance of IMT measurements performed at different carotid sites. METHODS: Eighty-nine subjects ≤45 years were studied (55 with known CAD and 34 controls). IMT measurements were performed at the common carotid (CC), bulb and internal branch (IB) of both carotid arteries, (2112 measures). The diagnostic performance of IMT measurements performed at different sites, regarding the presence of CAD, was evaluated with ROC curves. RESULTS: Carotid plaques were found in 20.0% of the patients and 6.0% of the controls. The diagnostic performance of carotid IMT measures obtained at the CC, bulb or IB was not significantly different, with the CC and IB being slightly better (AUC ROC =0.82 and 0.80 respectively). CONCLUSIONS: IMT measures obtained at different carotid sites are associated with CAD in young (≤45 years) individuals. The diagnostic performance of IMT measured at the CC and IB is the more accurate measure, and this may be the most adequate for the measurement of IMT in this population.

Prognostic value of myocardium perfusion imaging with a new reconstruction algorithm.

BACKGROUND: It has been demonstrated that a new reconstruction algorithm for myocardium perfusion imaging (MPI) allows faster acquisition with similar accuracy. The prognostic value of MPI performed with this software and short acquisition time is unknown. METHODS: To determine the prognostic value we followed 3184 consecutive MPI patients between March 2008 and March 2010. A 2-day protocol with low dose 99mTc-MIBI (10-12 mCi) and a 6-minute acquisition was used. Exercise stress was used in 62.6% of the studies. Scans were reconstructed using the software "Evolution for cardiac". Perfusion defects were quantified by summed stress score (SSS) and categorized in four groups: SSS0 = 0; SSS1 = 1-3; SSS2 = 4-8; and SSS3 ≥ 9. Patients were phone contacted every 6 months for follow up and hard events were defined as death or myocardial infarction (MI) and total events as hard events plus late revascularization. RESULTS: The mean radiation dose was <7 mSv/patient. Mean F/U was 33 ± 20 months; 140 of the patients were lost to follow up and 86 were censored due early revascularization (<60 days after MPS). There were 140 hard events: 89 deaths and 51 MI. Mean age was 61.5 ± 12.3 years and 57.7% were male. Hard event rate was 0.8%/year in patients with normal MPS and 3.7%/year in those with abnormal MPS. Patients with larger defects had nine times more hard events than patients with SSS = 0 (14.2% vs 1.6%). Revascularization was more frequent in patients with abnormal MPS than normal MPS (21.7% vs 3.9%; P < 0.001). Cox proportional hazard analysis showed that SSS was an independent predictor of hard events and revascularization. CONCLUSIONS: The use of reduced-dose, fast myocardial perfusion SPECT and the new processing algorithm lowers acquisition time and radiation exposure compared to conventional SPECT without compromising the well-established prognostic value of MPI.

DNA damage and repair in patients undergoing myocardial perfusion single-photon emission computed tomography.

As patient exposure to ionizing radiation from medical imaging and its risks are continuing issues, this study aimed to evaluate DNA damage and repair markers after myocardial perfusion single-photon emission computed tomography (MPS). Thirty-two patients undergoing Tc-99m sestamibi MPS were studied. Peripheral blood was collected before radiotracer injection at rest and 60-90 min after injection. The comet assay (single-cell gel electrophoresis) was performed with peripheral blood cells to detect DNA strand breaks. Three descriptors were evaluated: the percentage of DNA in the comet tail, tail length, and tail moment (the product of DNA tail percentage and tail length). Quantitative PCR (qPCR) was performed to evaluate the expression of five genes related to signaling pathways in response to DNA damage and repair (ATM, ATR, BRCA1, CDKN1A, and XPC). Mann-Whitney's test was employed for statistical analysis; p < 0.05 was considered significant. Mean Tc-99m sestamibi dose was 15.1 mCi. After radiotracer injection, comparing post-exposure to pre-exposure samples of each of the 32 patients, no statistically significant differences of the DNA percentage in the tail, tail length or tail moment were found. qPCR revealed increased expression of BRCA1 and XPC, without any significant difference regarding the other genes. No significant increase in DNA strand breaks was detected after a single radiotracer injection for MPS. There was activation of only two repair genes, which may indicate that, in the current patient sample, the effects of ionizing radiation on the DNA were not large enough to trigger intense repair responses, suggesting the absence of significant DNA damage.

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.

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.

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.

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.

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.