Identifying consistent echocardiographic thresholds for risk stratification in pulmonary arterial hypertension.

Several indices of right heart remodeling and function have been associated with survival in pulmonary arterial hypertension (PAH). Outcome analysis and physiological relationships between variables may help develop a consistent grading system. Patients with Group 1 PAH followed at Stanford Hospital who underwent right heart catheterization and echocardiography within 2 weeks were considered for inclusion. Echocardiographic variables included tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (RVFAC), free wall strain (RVFWS), RV dimensions, and right atrial volumes. The main outcome consisted of death or lung transplantation at 5 years. Mathematical relationships between variables were determined using weighted linear regression and severity thresholds for were calibrated to a 20% 1-year mortality risk. PAH patients (n = 223) had mean (SD) age of 48.1 (14.1) years, most were female (78%), with a mean pulmonary arterial pressure of 51.6 (13.8) mmHg and pulmonary vascular resistance index of 22.5(6.3) WU/m2. Measures of right heart size and function were strongly related to each other particularly RVFWS and RVFAC (R 2 = 0.82, p < 0.001), whereas the relationship between TAPSE and RVFWS was weaker (R 2 = 0.28, p < 0.001). Death or lung transplantation at 5 years occurred in 78 patients (35%). Guided by outcome analysis, we ascertained a uniform set of parameter thresholds for grading the severity of right heart adaptation in PAH. Using these quantitative thresholds, we, then, validated the recently reported REVEAL-echo score (AUC 0.68, p < 0.001). This study proposes a consistent echocardiographic grading system for right heart adaptation in PAH guided by outcome analysis.

3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension.

BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure. METHODS: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function. RESULTS: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments. CONCLUSIONS: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.

Improving Reporting of Exercise Capacity Across Age Ranges Using Novel Workload Reference Equations.

Exercise capacity (EC) is an important predictor of survival in the general population and in subjects with cardiopulmonary disease. Despite its relevance, considering the percent-predicted workload (%pWL) given by current equations may overestimate EC in older adults. Therefore, to improve the reporting of EC in clinical practice, our main objective was to develop workload reference equations (pWL) that better reflect the relation between workload and age. Using the Fitness Registry and the Importance of Exercise National Database (FRIEND), we analyzed a reference group of 6,966 apparently healthy participants and 1,060 participants with heart failure who underwent graded treadmill cardiopulmonary exercise testing. For the first group, the mean age was 44 years (18 to 79); 56.5% of participants were males and 15.4% had obesity. Peak oxygen consumption was 11.6 ± 3.0 METs in males and 8.5 ± 2.4 METs in females. After partition analysis, we first developed sex-specific pWL equations to allow comparisons to a healthy weight reference. For males, pWL (METs) = 14.1-0.9×10-3×age2 and 11.5-0.87×10-3×age2 for females. We used those equations as denominators of %pWL, and based on their distribution, we determined thresholds for EC classification, with average EC defined by the range corresponding to 85% to 115%pWL. Compared with %pWL using current equations, the new equations yielded better-calibrated %pWL across different age ranges. We also derived body mass index-adjusted pWL equations that better assessed EC in subjects with heart failure. In conclusion, the novel pWL equations have the potential to impact the report of EC in practice.

Clinical and biochemical predictors of longitudinal changes in left atrial structure and function: A general population study.

PURPOSE: There is a need for better understanding the factors that modulate left atrial (LA) dysfunction. Therefore, we determined associations of clinical and biochemical biomarkers with serial changes in echocardiographic indexes of LA function in the general population. METHODS: We measured LA maximal and minimal volume indexes (LAVImax and LAVImin) by echocardiography and LA reservoir strain (LARS) by two-dimensional speckle-tracking in 627 participants (mean age 50.8 years, 51.2% women) at baseline and after 4.8 years. RESULTS: During follow-up, LARS decreased significantly in men (-.90%, P = .033) but not in women (-.23%, P = .60). In stepwise regression analysis, stronger decrease in LARS over time was associated with male sex, a higher age, body mass index (BMI), mean arterial pressure (MAP) and serum insulin at baseline and with a greater increase in BMI and MAP over time (P ≤ .018). Similarly, an increased risk of developing or retaining abnormal LARS was observed in older participants, in subjects with a higher baseline BMI, MAP, heart rate (HR), troponin T and ΔMAP, and in those who used ß-blockers at baseline. Both LAVImax and LAVImin increased significantly over time (P ≤ .0007). This increase was associated with a higher baseline age, pulse pressure and a lower HR at baseline and a greater increase in pulse pressure over time (P ≤ .029). Higher serum insulin and D-dimer were independently associated with a stronger increase in LAVImin (P ≤ .0034). CONCLUSION: Subclinical worsening in LA dysfunction was associated with older age, hypertension, obesity, insulin resistance and troponin T levels. Cardiovascular risk management strategies may delay LA deterioration.

Feature-based clustering of the left ventricular strain curve for cardiovascular risk stratification in the general population.

Objective: Identifying individuals with subclinical cardiovascular (CV) disease could improve monitoring and risk stratification. While peak left ventricular (LV) systolic strain has emerged as a strong prognostic factor, few studies have analyzed the whole temporal profiles of the deformation curves during the complete cardiac cycle. Therefore, in this longitudinal study, we applied an unsupervised machine learning approach based on time-series-derived features from the LV strain curve to identify distinct strain phenogroups that might be related to the risk of adverse cardiovascular events in the general population. Method: We prospectively studied 1,185 community-dwelling individuals (mean age, 53.2 years; 51.3% women), in whom we acquired clinical and echocardiographic data including LV strain traces at baseline and collected adverse events on average 9.1 years later. A Gaussian Mixture Model (GMM) was applied to features derived from LV strain curves, including the slopes during systole, early and late diastole, peak strain, and the duration and height of diastasis. We evaluated the performance of the model using the clinical characteristics of the participants and the incidence of adverse events in the training dataset. To ascertain the validity of the trained model, we used an additional community-based cohort (n = 545) as external validation cohort. Results: The most appropriate number of clusters to separate the LV strain curves was four. In clusters 1 and 2, we observed differences in age and heart rate distributions, but they had similarly low prevalence of CV risk factors. Cluster 4 had the worst combination of CV risk factors, and a higher prevalence of LV hypertrophy and diastolic dysfunction than in other clusters. In cluster 3, the reported values were in between those of strain clusters 2 and 4. Adjusting for traditional covariables, we observed that clusters 3 and 4 had a significantly higher risk for CV (28% and 20%, P ≤ 0.038) and cardiac (57% and 43%, P ≤ 0.024) adverse events. Using SHAP values we observed that the features that incorporate temporal information, such as the slope during systole and early diastole, had a higher impact on the model's decision than peak LV systolic strain. Conclusion: Employing a GMM on features derived from the raw LV strain curves, we extracted clinically significant phenogroups which could provide additive prognostic information over the peak LV strain.

Percepções de profissionais da psicologia sobre sua atuação no sistema socioeducativo / Perceptions of psychology professionals about their performance in the socioeducational system

O objetivo do estudo foi compreender quais eram as percepções das(os) profissionais da Psicologia que trabalham no Sistema Socioeducativo sobre a sua atuação dentro dos Centros de Atendimentos Socioeducativos (CASEs) do Complexo Pomeri em Cuiabá, Mato Grosso. Foram entrevistadas 14 pessoas que atuavam como profissionais da área de Psicologia no Sistema Socioeducativo, os dados foram organizados/analisados utilizando os critérios da Análise de Conteúdo de Bardin. Foram identificadas diversas percepções sobre a atuação das(os) profissionais da Psicologia neste contexto de trabalho dos CASEs, evidenciando o que pensam, sentem e imaginam as pessoas entrevistadas. Como principais resultados, identificamos percepções que denunciaram as mazelas do Sistema Socioeducativo (explicitando as faces mais tristes da privação de liberdade de adolescentes em cumprimento de medida socioeducativa), bem como percepções que evidenciam o compromisso ético das(os) profissionais da Psicologia que atuam nos CASEs. Ficou evidente que, apesar das dificuldades, é possível desenvolver uma prática profissional da Psicologia no contexto da socioeducação, trabalhando em prol dos direitos dos adolescentes e da construção de uma práxis psicológica qualificadamente socioeducativa.

The objective of the study was to understand the perceptions psychologists working in the Socioeducational System about their performance in the Socio-educational Service Centers (CASEs) of the Pomeri Complex in Cuiabá, Mato Grosso, Brazil. Fourteen people who worked as professionals in the field of Psychology in the Socio-educational System were interviewed, and the data were organized/analyzed using the criteria of Bardin's Content Analysis. Different perceptions were identified about the role of psychology professionals in this context of the work of the CASEs, showing what the interviews think, feel, and imagine. The main results, we identified perceptions denouncing the abuses of the Socio-educational System (explaining the saddest faces of the deprivation of liberty of adolescents in compliance with socio-educational measures), as well as perceptions that evidence the ethical commitment of Psychology professionals who work in CASEs. It was evident that, despite the difficulties, it is possible to develop a professional practice of Psychology in the context of socio-education, working toward the rights of adolescents and the construction of a qualified socio-educational psychological praxis.

Right Ventricular Dysfunction Patterns among Patients with COVID-19 in the Intensive Care Unit: A Retrospective Cohort Analysis.

Rationale: Right ventricular (RV) dysfunction is common among patients hospitalized with coronavirus disease (COVID-19); however, its epidemiology may depend on the echocardiographic parameters used to define it. Objectives: To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among patients with COVID-19 admitted to the intensive care unit (ICU), as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality. Methods: We conducted a retrospective cohort study of ICU patients with COVID-19 between March 4, 2020, and March 4, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation, respectively, were defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality was assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at the time of transthoracic echocardiogram, and Acute Physiology and Chronic Health Evaluation II score. Results: A total of 116 patients were included, of whom 69% had RV dysfunction by one or more parameters, and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction were the presence of three abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RV fractional area change (24% vs. 36%; P = 0.001), worse RVFWS (16.3% vs. 19.1%; P = 0.005), higher RV systolic pressure (45 mm Hg vs. 31 mm Hg; P = 0.001) but similar TAPSE (13 mm vs. 13 mm; P = 0.30) compared with those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (odds ratio, 2.91; 95% confidence interval, 1.01-9.44), as was the presence of at least two parameter abnormalities. Conclusions: ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

Novel left ventricular mechanical index in pulmonary arterial hypertension.

Ventricular interdependence plays an important role in pulmonary arterial hypertension (PAH). It can decrease left ventricular (LV) longitudinal strain (LVLS) and lead to a leftward displacement ("transverse shortening") of the interventricular septum (sTS). For this study, we hypothesized the ratio of LVLS/sTS would be a sensitive marker of systolic ventricular interactions in PAH. In a cross-sectional cohort of patients with PAH (n = 57) and matched controls (n = 57), we quantified LVLS and septal TS in the amplitude and time domain. We then characterized LV phenotypes using upset plots, ventricular interactions using network analysis, and longitudinal analysis in a representative cohort of 45 patients. We also measured LV metrics in mice subjected to pulmonary arterial banding (PAB) using a 7 T magnetic resonance imaging at baseline, Week 1, and Week 7 post-PAB (N = 9). Patients with PAH had significantly reduced absolute LVLS (15.4 ± 3.4 vs. 20.1 ± 2.3%, p < 0.0001), higher sTS (53.0 ± 12.2 vs. 28.0 ± 6.2%, p < 0.0001) and lower LVLS/sTS (0.30 ± 0.09 vs. 0.75 ± 0.16, p < 0.0001) compared to controls. Reduced LVLS/sTS was observed in 89.5% of patients, while diastolic dysfunction, impaired LVLS (<16%), and LV atrophy were observed in 73.7%, 52.6%, and 15.8%, respectively. In the longitudinal cohort, changes in LVLS/sTS were closely associated with changes in N-terminal pro B-type natriuretic peptide (r = 0.73, p < 0.0001) as well as survival. Mice subjected to PAB showed significant RV systolic dysfunction and decreased LVLS/sTS compared to sham animals. We conclude that in PAH, LVLV/sTS is a simple ratio that can reflect ventricular systolic interactions.

Challenging obesity and sex based differences in resting energy expenditure using allometric modeling, a sub-study of the DIETFITS clinical trial.

BACKGROUND & AIMS: Resting energy expenditure (REE) is a major component of energy balance. While REE is usually indexed to total body weight (BW), this may introduce biases when assessing REE in obesity or during weight loss intervention. The main objective of the study was to quantify the bias introduced by ratiometric scaling of REE using BW both at baseline and following weight loss intervention. DESIGN: Participants in the DIETFITS Study (Diet Intervention Examining The Factors Interacting with Treatment Success) who completed indirect calorimetry and dual-energy X-ray absorptiometry (DXA) were included in the study. Data were available in 438 participants at baseline, 340 at 6 months and 323 at 12 months. We used multiplicative allometric modeling based on lean body mass (LBM) and fat mass (FM) to derive body size independent scaling of REE. Longitudinal changes in indexed REE were then assessed following weight loss intervention. RESULTS: A multiplicative model including LBM, FM, age, Black race and the double product (DP) of systolic blood pressure and heart rate explained 79% of variance in REE. REE indexed to [LBM0.66 × FM0.066] was body size and sex independent (p = 0.91 and p = 0.73, respectively) in contrast to BW based indexing which showed a significant inverse relationship to BW (r = -0.47 for female and r = -0.44 for male, both p < 0.001). When indexed to BW, significant baseline differences in REE were observed between male and female (p < 0.001) and between individuals who are overweight and obese (p < 0.001) while no significant differences were observed when indexed to REE/[LBM0.66 × FM0.066], p > 0.05). Percentage predicted REE adjusted for LBM, FM and DP remained stable following weight loss intervention (p = 0.614). CONCLUSION: Allometric scaling of REE based on LBM and FM removes body composition-associated biases and should be considered in obesity and weight-based intervention studies.

Retratamento endodôntico de um primeiro pré-molar superior com três canais – relato de caso / Endodontic retreatment of a first upper premolar with three canals – a case report

O presente trabalho relata o caso clínico de uma paciente com leve sensibilidade e presença de fístula no primeiro pré-molar superior direito, que já tinha sido submetido a tratamento endodôntico com complementação cirúrgica. O exame radiográfico revelou um erro de diagnóstico na identificação do número de canais, uma vez que era possível identificar a presença de três canais e três raízes no referido elemento, sendo que apenas os canais disto-vestibular e palatino encontravam-se preenchidos com material obturador, enquanto o canal mésio-vestibular, além de vazio, tinha no ápice a presença de material radiopaco. Restabeleceu-se uma cavidade de acesso e remoção do material obturador com o auxílio de uma broca de Gates-Glidden número 3, dos terços médio e cervical, e com uma lima do tipo Kerr número 25 combinada com o solvente Eucaliptol, do terço apical. Após a realização do preparo biomecânico pela Técnica Mista Invertida, promoveu-se a renovação de variadas substâncias como curativo de demora, por um período que se estendeu por 30 dias. Contudo, não foi possível observar regressão da fístula, o que motivou a realização da obturação dos canais radiculares promovendo-se um extravasamento proposital de material obturador através do forame apical removido através de uma curetagem apical. Ao longo de 16 meses, um acompanhamento clínico e radiográfico revelou o desaparecimento do trajeto fistuloso, ausência de sensibilidade à palpação e/ou percussão e restauração da dimensão normal do espaço periodontal, caracterizando o sucesso do tratamento realizado.

The present work reports a clinical case of a patient with light sensibility and fistula presence in the right maxillary first premolar that had already been submitted to endodontic treatment with surgical complementation. The radiographic exam revealed a diagnosis misinterpretation in the identification of the number of canals, once it was possible to identify the presence of three canals and three roots in the referred element, and just the distobuccal and palatine canals were filled out with endodontic material, while the mesiobuccal canal, was not only empty, but there was also the presence of radiopaque material in the apex. It was recovered an access cavity and the material was removed through a Gates-Glidden drill number 3, by medium and cervical thirds, and a file type Kerr number 25 combined with the solvent Eucalyptol of the apical third. After the accomplishment of the biomechanical preparation for the Inverted Mixed Technique, the renewal varied substances was promoted as a delay curative, for a period that extended for 30 days. As it was not possible to observe regression of the fistula, the accomplishment of the filling of the root canals was realized and it brought along a deliberate extrude of material through the apical foramen that was removed through a curettage apical. For the next 16 months a clinical and radiographic attendance revealed the disappearance of the fistulous itinerary, a sensibility absence in palpation and/or percussion and restoration of the normal dimension of the periodontal space characterizing the success of the accomplished treatment.