Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction.

AIMS: Elevated left atrial (LA) pressure is a pathophysiologic hallmark of heart failure with preserved ejection fraction (HFpEF). Chronically elevated LA pressure leads to LA enlargement, which may impair LA function and increase pulmonary pressures. We sought to evaluate the relationship between LA volume and pulmonary arterial haemodynamics in patients with HFpEF. METHODS AND RESULTS: Data from 85 patients (aged 69 ± 8 years) who underwent exercise right heart catheterization and echocardiography were retrospectively analysed. All had symptoms of heart failure, left ventricular ejection fraction ≥50% and haemodynamic features of HFpEF. Patients were divided into LA volume index-based tertiles (≤34 ml/m2 , >34 to ≤45 ml/m2 , >45 ml/m2 ). A subgroup analysis was performed in patients with recorded LA global reservoir strain (n = 60), with reduced strain defined as ≤24%. Age, sex, body surface area and left ventricular ejection fraction were similar between volume groups. LA volume was associated with blunted increases in cardiac output with exercise (padjusted <0.001), higher resting mean pulmonary artery pressure (padjusted  = 0.003), with similar wedge pressure (padjusted  = 1). Pulmonary vascular resistance (PVR) increased with increasing LA volume (padjusted <0.001). Larger LA volumes featured reduced LA strain (padjusted <0.001), with reduced strain associated with reduced PVR-compliance time (0.34 [0.28-0.40] vs. 0.38 [0.33-0.43], p = 0.03). CONCLUSION: Increasing LA volume may be associated with more advanced pulmonary vascular disease in HFpEF, featuring higher PVR and pulmonary pressures. Reduced LA function, worse at increasing LA volumes, is associated with a disrupted PVR-compliance relationship, further augmenting impaired pulmonary haemodynamics.

Ciência e Covid-19: a construção de programas de pesquisa científica frente a cenários complexos e em contraponto ao contexto negacionista / Science and Covid-19: the construction of scientific research programs in view of complex scenarios and in counterpoint to the denialist context

Resume O papel que a ciência tem cumprido em relação à pandemia da Covid-19 está em franca discussão no Brasil e no mundo. Considerando a necessidade de aprofundar o debate sobre as concepções de ciência no presente contexto, assim como suas consequências, o objetivo deste ensaio é discutir, a partir de referenciais da epistemologia, o problema da demarcação entre ciência e não ciência, os programas de pesquisa científica e o negacionismo na pandemia. Na primeira parte do texto, apresenta-se a discussão da demarcação entre ciência e não ciência, com destaque para a proposição do filósofo Imre Lakatos sobre os programas de pesquisa científica e sua relação com as pesquisas sobre a Covid-19. Na segunda parte, argumenta-se sobre o negacionismo na pandemia da Covid-19 e sua relação com a necropolítica e o neofascismo. Por fim, discute-se a necessidade de incorporação da interdisciplinaridade, participação ativa dos sujeitos e garantia dos direitos humanos em programas de pesquisa científica sobre a Covid-19, assim como em outros temas de saúde pública.

Abstract The role that science has played in relation to the Covid-19 pandemic is in frank discussion in Brazil and in the world. Considering the need to deepen the debate on the conceptions of science in the present context, as well as its consequences, this essay aims to discuss, from epistemological references, the problem of the demarcation between science and non-science, scientific research programs and denialism in the pandemic. In the first part of the text, the discussion of the demarcation between science and non-science is presented, with emphasis on the proposition of philosopher Imre Lakatos on scientific research programs and their relationship with research on Covid-19. In the second part, an argument is made about denialism in the Covid-19 pandemic and its relationship with necropolitics and neo-fascism. Finally, the need to incorporate interdisciplinarity, the active participation of subjects and the guarantee of human rights in scientific research programs on Covid-19, as well as in other public health topics, is discussed.Resumo: O papel que a ciência tem cumprido em relação à pandemia da Covid-19 está em franca discussão no Brasil e no mundo. Considerando a necessidade de aprofundar o debate sobre as concepções de ciência no presente contexto, assim como suas consequências, o objetivo deste ensaio é discutir, a partir de referenciais da epistemologia, o problema da demarcação entre ciência e não ciência, os programas de pesquisa científica e o negacionismo na pandemia. Na primeira parte do texto, apresenta-se a discussão da demarcação entre ciência e não ciência, com destaque para a proposição do filósofo Imre Lakatos sobre os programas de pesquisa científica e sua relação com as pesquisas sobre a Covid-19. Na segunda parte, argumenta-se sobre o negacionismo na pandemia da Covid-19 e sua relação com a necropolítica e o neofascismo. Por fim, discute-se a necessidade de incorporação da interdisciplinaridade, participação ativa dos sujeitos e garantia dos direitos humanos em programas de pesquisa científica sobre a Covid-19, assim como em outros temas de saúde pública.

Left atrial strain predicts cardiovascular response to exercise in young adults with suboptimal blood pressure.

AIMS: To investigate the left ventricular response to exercise in young adults with hypertension, and identify whether this response can be predicted from changes in left atrial function at rest. METHODS: A total of 127 adults aged 18-40 years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n = 68) and optimal blood pressure <120/80mm Hg (n = 59). Left ventricular systolic function during exercise was obtained from an apical four chamber view, while resting left atrial function was assessed from apical four and two chamber views. RESULTS: Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response ( ß = .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure. CONCLUSION: Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension.

Impaired myocardial reserve underlies reduced exercise capacity and heart rate recovery in preterm-born young adults.

AIMS: We tested the hypothesis that the known reduction in myocardial functional reserve in preterm-born young adults is an independent predictor of exercise capacity (peak VO2) and heart rate recovery (HRR). METHODS AND RESULTS: We recruited 101 normotensive young adults (n = 47 born preterm; 32.8 ± 3.2 weeks' gestation and n = 54 term-born controls). Peak VO2 was determined by cardiopulmonary exercise testing (CPET), and lung function assessed using spirometry. Percentage predicted values were then calculated. HRR was defined as the decrease from peak HR to 1 min (HRR1) and 2 min of recovery (HRR2). Four-chamber echocardiography views were acquired at rest and exercise at 40% and 60% of CPET peak power. Change in left ventricular ejection fraction from rest to each work intensity was calculated (EFΔ40% and EFΔ60%) to estimate myocardial functional reserve. Peak VO2 and per cent of predicted peak VO2 were lower in preterm-born young adults compared with controls (33.6 ± 8.6 vs. 40.1 ± 9.0 mL/kg/min, P = 0.003 and 94% ± 20% vs. 108% ± 25%, P = 0.001). HRR1 was similar between groups. HRR2 decreased less in preterm-born young adults compared with controls (-36 ± 13 vs. -43 ± 11 b.p.m., P = 0.039). In young adults born preterm, but not in controls, EFΔ40% and EFΔ60% correlated with per cent of predicted peak VO2 (r2 = 0.430, P = 0.015 and r2 = 0.345, P = 0.021). Similarly, EFΔ60% correlated with HRR1 and HRR2 only in those born preterm (r2 = 0.611, P = 0.002 and r2 = 0.663, P = 0.001). CONCLUSIONS: Impaired myocardial functional reserve underlies reductions in peak VO2 and HRR in young adults born moderately preterm. Peak VO2 and HRR may aid risk stratification and treatment monitoring in this population.

Changes in the Preterm Heart From Birth to Young Adulthood: A Meta-analysis.

CONTEXT: Preterm birth is associated with incident heart failure in children and young adults. OBJECTIVE: To determine the effect size of preterm birth on cardiac remodeling from birth to young adulthood. DATA SOURCES: Data sources include Medline, Embase, Scopus, Cochrane databases, and clinical trial registries (inception to March 25, 2020). STUDY SELECTION: Studies in which cardiac phenotype was compared between preterm individuals born at <37 weeks' gestation and age-matched term controls were included. DATA EXTRACTION: Random-effects models were used to calculate weighted mean differences with corresponding 95% confidence intervals. RESULTS: Thirty-two observational studies were included (preterm = 1471; term = 1665). All measures of left ventricular (LV) and right ventricular (RV) systolic function were lower in preterm neonates, including LV ejection fraction (P = .01). Preterm LV ejection fraction was similar from infancy, although LV stroke volume index was lower in young adulthood. Preterm LV peak early diastolic tissue velocity was lower throughout development, although preterm diastolic function worsened with higher estimated filling pressures from infancy. RV longitudinal strain was lower in preterm-born individuals of all ages, proportional to the degree of prematurity (R 2 = 0.64; P = .002). Preterm-born individuals had persistently smaller LV internal dimensions, lower indexed LV end-diastolic volume in young adulthood, and an increase in indexed LV mass, compared with controls, of 0.71 g/m2 per year from childhood (P = .007). LIMITATIONS: The influence of preterm-related complications on cardiac phenotype could not be fully explored. CONCLUSIONS: Preterm-born individuals have morphologic and functional cardiac impairments across developmental stages. These changes may make the preterm heart more vulnerable to secondary insults, potentially underlying their increased risk of early heart failure.

Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction.

BACKGROUND: Elevated left atrial (LA) pressure, particularly during exercise, is associated with symptomatic status and survival in patients with heart failure with preserved ejection fraction (HFpEF). We aimed to characterize the contribution of abnormal LA mechanical properties to exercise haemodynamics in HFpEF. METHODS AND RESULTS: Simultaneous echocardiography and right heart catheterization were performed in 71 subjects with left ventricular ejection fraction ≥ 50% referred for assessment of exertional dyspnoea. According to haemodynamic evaluation, 49 patients were diagnosed with HFpEF [pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg at rest and/or ≥ 25 mmHg at maximal exertion] and 22 as non-cardiac dyspnoea. Apical two- and four-chamber views were used for blinded two-dimensional LA speckle tracking analysis. HFpEF was characterized by impaired LA reservoir (24.3 ± 9.6 vs. 36.7 ± 8.4%, P < 0.001) and pump strain (-11.5 ± 3.2 vs. -17.0 ± 3.4%, P < 0.001); and increased stiffness (0.8 ± 0.7 vs. 0.2 ± 0.1 mmHg/%, P < 0.001). Reservoir and pump strain correlated with exercise PCWP (r = -0.64 and r = 0.72, P < 0.001), and remained independent predictors after adjusting for left ventricular mass index, LA volume index, mean E/e' and systolic blood pressure (B = -0.66 and B = 1.41, respectively, P < 0.001). LA stiffness was strongly related to B-type natriuretic peptide levels (r = 0.73, P < 0.001; B = 173.0, P < 0.001). Reservoir strain at cut-off of ≤ 33% predicted invasively verified HFpEF diagnosis with 88% sensitivity and 77% specificity, providing a net reclassification improvement of 12% in comparison to the 2016 European Society of Cardiology criteria for non-invasive diagnosis of HFpEF. CONCLUSIONS: Impaired LA reservoir and pump function and increased stiffness are associated with abnormal exercise haemodynamics in HFpEF. These markers provide significant HFpEF diagnostic utility in elderly ambulatory patients with dyspnoea.

Direitos humanos e saúde: 70 anos após a Declaração Universal dos Direitos Humanos / Human rights and health: seventy years after the Universal Declaration of Human Rights / Derechos humanos y salud: setenta años después de la Declaración Universal de los Derechos Humanos

A presente nota apresenta a discussão sobre a Declaração Universal dos Direitos Humanos desde sua assinatura em 1948, questionando a sua efetividade na luta por direitos e reconhecendo suas falhas ao que se refere a igualdade entre os sujeitos. Dessa forma ressalta os apagamentos que se escondem por trás de uma dita "universalidade" e reivindica a necessidade do debate, primeiramente, por dignidade ­ conceito que se torna inseparável do que se entende de fato por Direitos.

This note shows the discussion on the Universal Declaration of Human Rights since its adoption in 1948, questioning its effectiveness in the struggle for rights and acknowledging its failures on the equality between the individuals. In this way, the deletions hidden behind a so-called "universality" are highlighted, claiming first, the need of debating for dignity ­ a concept that becomes inseparable from what is in fact understood by Rights.

La presente nota presenta la discusión sobre la Declaración Universal de los Derechos Humanos desde que fue adoptada en 1948, cuestionando su efectividad en la lucha por derechos y reconociendo sus fallas cuando refiriéndose a la igualdad entre los sujetos. De esa forma, se resalta la supresión que se esconde por detrás de una dicha "universalidad" y reivindica la necesidad del debate, primeramente, por dignidad ­ concepto que se torna inseparable de lo que se entiende de of ahecho por Derechos.

Imaging and Management of Heart Failure and Preserved Ejection Fraction.

PURPOSE OF REVIEW: The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising and in some places, it is already the most prevalent form of heart failure. The usual treatments of HF do not improve mortality or outcomes in HFpEF, suggesting a distinct pathophysiology that remains poorly characterized. The neutrality of clinical trial results is also attributable to the heterogeneity of patient profiles, and by poor characterization offered by classical echocardiography parameters. Emerging imaging modalities may overcome this problem. We therefore aimed to summarize recent advances offered by cardiovascular imaging in disease characterization, and the implication of findings to new phenotype-specific treatment options. RECENT FINDINGS: Novel cardiovascular imaging techniques such as LV global longitudinal strain, left atrial strain, tissue characterization by magnetic resonance T1 time, as well as incorporation of systolic and diastolic stress testing offer greatly improved characterization, diagnosis, and stratification of disease pathogenesis. These techniques offer insight into identification of HFpEF sub-phenotypes that are resistant to, or responsive to therapies. There is a growing body of evidence that novel cardiovascular imaging modalities are able to characterize HFpEF patients with much greater accuracy than current guideline-driven parameters. Whether this information can be synthesized to adequately stratify patients into sub-phenotypes with clearer disease pathogenesis amenable to targeted intervention will be of particular future interest.

Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born Adults.

BACKGROUND: Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk. OBJECTIVES: The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise. METHODS: We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing. RESULTS: Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/m2 vs. 1,669 ± 937 ml/min/m2; p = 0.021). LV length and resting peak systolic longitudinal strain predicted EF increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p = 0.009 and r = 0.56, p = 0.031, respectively). CONCLUSIONS: Preterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231).

Experimental model of glucocorticoid-induced insulin resistance.

PURPOSE:: To evaluate metabolic effects in experimental model of glucocorticoid-induced insulin resistance. METHODS:: Twenty Wistar male rats were randomly divided into two groups, which were treated with intraperitoneally injected dexamethasone 1mg/Kg/day for ten days consecutively (Group D; n=10) and placebo (Group C; n=10). The variables analyzed were: from the first to the 10th day - body weight (before and after treatment); food and water daily consumption; on the 10th day - glycemia, insulinemia, HOMA-beta and HOMA-IR. The blood samples for laboratory analysis were obtained by intracardiac puncture. Also on the 10th day liver fragments were taken for analyzing glycogen and fattty. RESULTS:: Group D animals compared to group C had: weight reduction (g), (D=226.5±24.7 vs C=295.0±25.4; p=0.001); increased glycemia (mmol/l) (D=19.5±2.1 vs C=14.2±3.1; p=0.0001); diminished insulinemia (mU/l) (D=0.2±0.1 vs C=2.0±0.4; p=0.0001); reduced HOMA-ß (D=0.2±0.1 vs C=4.2±1.7; p=0.0002); diminished HOMA-IR (D=0.2±0.1 vs C=1.3±0.4; p=0.0002). Histological examination of the liver showed that 100% of group D and none of group C had moderate fatty. (p=0.2). CONCLUSION:: Animals treated with glucocorticoid, in this experimental model, expressed hyperglycemia, hypoinsulinism and decreased peripheral insulin sensitivity.

Experimental model of glucocorticoid-induced insulin resistance

ABSTRACT PURPOSE: To evaluate metabolic effects in experimental model of glucocorticoid-induced insulin resistance. METHODS: Twenty Wistar male rats were randomly divided into two groups, which were treated with intraperitoneally injected dexamethasone 1mg/Kg/day for ten days consecutively (Group D; n=10) and placebo (Group C; n=10). The variables analyzed were: from the first to the 10th day - body weight (before and after treatment); food and water daily consumption; on the 10th day - glycemia, insulinemia, HOMA-beta and HOMA-IR. The blood samples for laboratory analysis were obtained by intracardiac puncture. Also on the 10th day liver fragments were taken for analyzing glycogen and fattty. RESULTS: Group D animals compared to group C had: weight reduction (g), (D=226.5±24.7 vs C=295.0±25.4; p=0.001); increased glycemia (mmol/l) (D=19.5±2.1 vs C=14.2±3.1; p=0.0001); diminished insulinemia (mU/l) (D=0.2±0.1 vs C=2.0±0.4; p=0.0001); reduced HOMA-β (D=0.2±0.1 vs C=4.2±1.7; p=0.0002); diminished HOMA-IR (D=0.2±0.1 vs C=1.3±0.4; p=0.0002). Histological examination of the liver showed that 100% of group D and none of group C had moderate fatty. (p=0.2). CONCLUSION: Animals treated with glucocorticoid, in this experimental model, expressed hyperglycemia, hypoinsulinism and decreased peripheral insulin sensitivity.

Necessidade insatisfeita por métodos anticoncepcionais no Brasil / Unmet contraception needs in Brazil

No Brasil, a prevalência do uso de contraceptivo é elevada e a taxa de fecundidade total está quase no nível de reposição. No entanto, ainda há um percentual significativo de gravidezes indesejadas, abortos provocados e mulheres que não querem mais ter filhos ou querem tê-los mais tarde, porém não estão usando métodos contraceptivos - ou seja, mulheres com necessidade insatisfeita por anticoncepção. O objetivo deste estudo é apresentar a magnitude da necessidade insatisfeita por método anticoncepcional entre mulheres unidas no Brasil, assim como identificar os fatores a ela associados. A fonte de dados utilizada nesse estudo é proveniente da Pesquisa Nacional Sobre Demografia e Saúde, realizada no Brasil em 1996. Para identificar os determinantes associados com a necessidade insatisfeita por anticoncepção foi utilizado o modelo multinomial, em que a variável resposta tem três categorias: necessidade para espaçar, necessidade para limitar e sem necessidade. A análise empreendida ao longo deste trabalho revelou uma forte associação entre as variáveis relativas ao ciclo de vida das mulheres (idade e número de filhos) e a necessidade insatisfeita por métodos anticoncepcionais. Com relação às variáveis socioeconômicas destaca-se a elevada probabilidade de necessidade insatisfeita de limitar entre as mulheres da região Nordeste. Observou-se ainda que mulheres com maior nível de escolaridade são menos propensas a apresentar uma necessidade insatisfeita de limitar. A análise aponta para a necessidade de adequação e universalização dos serviços de planejamento familiar com vistas a um atendimento integral à saúde da mulher.

In Brazil the prevalence of use of contraceptives is high and the total fertility rate is almost at the replacement level. However, there still is a significant proportion of unwanted pregnancies, induced abortions, and women who do not want any more children, or those who want to postpone childbearing, but are not using any conceptive method, that is, women with an unmet contraceptive need. The objective of this study is to describe the magnitude of the unmet contraceptive needs among Brazilian married women, as well as to identify the factors associated with this need. The information used is from the National Demographics and Health Survey carried out in Brazil in 1996. In order to identify the determinants associated with the unmet contraceptive needs, a multinomial model was used, with the outcome variable classified into three categories: need for spacing births, need for limiting births, and no need. The analysis conducted along with this work showed a strong association between factors related to the life cycle (age and number of children) and unmet contraception needs. In relation to socioeconomic factors, the high likelihood of unmet contraceptive needs among women from the Northeast region stands out. It has also been shown that women with a higher educational level are less prone to have an unmet need for limiting births. The analysis points out the need of an appropriate and universal program for family planning services to assure full support to women's health.

Ensaio sobre a relaçäo epistemológica entre probabilidade e método científico / Essay on the epistemological relantionship between probability and scientific method

No século XIX, as regularidades observadas na contagem dos eventos surgem como a possibilidade de previsibilidade do que parecia até entäo imprevisível, principalmente no campo das Ciências Humanas e da Medicina. As leis probalísticas tornam-se uma alternativa para leis estritamente causais. Faz-se um breve histórico do cálculo de probabilidade e suas aplicaçöes, e desenvolveu-se algumas questöes filosóficas acerca da utilizaçäo da teoria da probabilidade e da análise de decisäo - oriunda do campo econômico - à Medicina.

Doença e tempo / Illness and time

Trata de um ensaio que procura estabelecer a propriedade da queståo: "Faz sentido conceber a doença como um fenómeno que transcende as categorias da representaçåo"? Destaca-se uma correspondência entre os fenômenos da representaçåo e da espacializaçåo. Representar passa a ser a atividade de definir uma trajetória que admite uma cronologia temporal de referência, onde um certo fenômeno é apresentado. O paradigma que define a "Anátomo-Clínica" e a Epidemiologia é considerado por nós como uma forma de representaçåo ou espacializaçåo da doença. Conclui ser possível o acesso a algo que se denomina "adoecer", que transcende a representaçåo "Anátomo-Clínica" e epidemiológica, desde que para tal, se admita a possibilidade de o conhecimento poder ser, também, construído fora do espaço, isto é, no tempo nåo-cronológico