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Daytime variation affects the tolerance of cardiomyocytes to ischemia–reperfusion injury (IRI). This study aims to evaluate the impact of time-of-day reperfusion on clinical outcomes of remote ischemic conditioning (RIC) as an adjuvant to primary percutaneous coronary intervention(PPCI) in ST-elevation myocardial infarction(STEMI) patients. A post-hoc analysis of a prospective, single-center parallel 1:1 randomized trial (RIC-STEMI) was performed. This analysis included 448 STEMI patients previously randomized to either PPCI alone (PPCI group) (n = 217) or RIC as an adjuvant to PPCI (RIC + PPCI group) (n = 231). Moreover, the sample was divided according to the time of PPCI: night-morning (22 h-11h59min) (n = 216) or afternoon (12 h-21h59min) (n = 232) groups. The primary follow-up endpoint was a composite of cardiac death and hospitalization due to heart failure. There were no significant differences in the clinical characteristics and the follow-up outcomes between groups. The afternoon period (HR = 0.474; 95% CI 0.230–0.977; p = 0.043) and RIC (HR = 0.423; 95% CI 0.195–0.917; p = 0.029) were independent predictors of the primary follow-up endpoint. An univariate analysis showed a lower frequency of primary follow-up endpoint, just in the afternoon period (10.3%vs0.9%; p = 0.002), in the RIC + PPCI group. A multivariate analysis revealed that RIC was an independent predictor of the primary follow-up endpoint in the afternoon group (HR = 0.098; 95% CI 0.012–0.785; p = 0.029), but not in the night-morning group. In addition, the afternoon period was not an independent predictor of the primary follow-up endpoint when the multivariate analysis was performed in the PPCI group. In conclusion, this study showed an important cardioprotective effect of RIC, namely in the afternoon period, suggesting that the afternoon period enhances the cardioprotection induced by RIC.

The urocortins (Ucns) belong to the corticotropin-releasing factor (CRF) family of peptides and have multiple effects within the central nervous and the cardiovascular systems. With growing evidence indicating significant cardioprotective properties and cardiovascular actions of these peptides, the question arises as to whether the plasma profiles of the Ucns are altered in pathologic settings. While reports have shown conflicting results and findings have not been corroborated in multiple independent cohorts, it seems likely that plasma Ucn concentrations are elevated in multiple cardiovascular conditions. The degree of increase and accurate determination of circulating values of the Ucns requires further validation.

New findings What is the central question of this study? Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF), nearly doubling the risk of death. Knowledge about the RV functional and structural changes in HFpEF and the effect of aerobic exercise is still limited and desirable to expand. What is the main finding and its importance? The HFpEF ZSF1 rat model presents RV structural and functional changes, mimicking the human condition. We show that aerobic exercise prevented the decline in VO2 max, lowered surrogate markers of RV overload (e.g., higher mean and maximum systolic pressure) and improved diastolic dysfunction (e.g., end-diastolic pressure and relaxation time constant). This knowledge emphasizes the importance of using exercise to manage HFpEF. Abstract Background : Right ventricular (RV) dysfunction is highly prevalent in HFpEF and is a marker of poor prognosis. We assessed the ZSF1 obese model of HFpEF to confirm if these rats also develop RV dysfunction and evaluated if aerobic exercise could prevent them. Methods and results ZSF1 obese rats were randomly allocated to aerobic exercise training group (n = 7; treadmill running, 5days/week, 60min/day, 15m/min, for 5 weeks) or to a sedentary group (n = 7). We also used ZSF1 lean rats (n = 7) as control group. After 5 weeks, rats were submitted to an exercise tolerance test, invasive hemodynamic evaluation, sacrificed and samples from RV were collected for histologic analysis. ZSF1 obese sedentary rats showed lower VO2 max, RV pressure-overload (e.g., higher mean and maximum systolic pressure) and diastolic dysfunction (e.g. higher minimal and end-diastolic pressurem and relaxation time constant), paralleled by RV cardiomyocyte hypertrophy. Except for cardiomyocyte hypertrophy, aerobic exercise prevented these functional changes.. Conclusions Our data supports that this model of HFpEF shows functional and structural changes in the RV that resemble the human HFpEF phenotype, reinforcing its utility to understand the pathophysiology and to adress novel therapeutic targets to manage HFpEF. In addition, we show that aerobic exercise is cardioprotective for the RV. A deeper knowledge of the mechanisms underlying the benefits of aerobic exercise could also lead to the identification of therapeutic targets to be further explored. This article is protected by copyright. All rights reserved.

Background In countries without organized population screening, incidental detection remains the major form of abdominal aortic aneurysm (AAA) diagnosis. Despite the presumed homogeneity in AAA prevalence, its rate of repair is highly variable, with Portugal treating 2 to 6 times fewer AAA per habitant than other western countries. Objectives To evaluate the detection rate and monitoring of incidental AAA in a multicentre cohort from Portuguese hospitals. Methods All abdominal CT scans performed in men ≥ 65 years old in three major Portuguese hospitals between January and June 2018 were selected for review. CT scans prescribed by the Vascular Surgery or Emergency Departments were excluded. Patients with previously known AAA were also excluded. Subjects with newly detected aneurysms were assessed for the two primary outcomes: the description of the finding by the radiologist in the written report; the effective follow-up recommendations by the prescriber of the CT or by the general practitioner (GP). Patients with newly found AAA that met criteria for monitoring or treatment and failed to be given guidance were contacted and included in surveillance programs. Results Overall, 3292 abdominal CT scans were selected for review. A total of 133 newly found aneurysms were detected (4.2% prevalence in the cohort). Of those, 48 cases (36%) were not described by the radiologist in the written report. Further 42 patients (32%) were not successfully oriented by the ordering physician or GP, despite having had their AAA mentioned. Overall, only 32% (n = 42) of the newly diagnosed AAA were correctly identified and referred to monitoring. Conclusions Incidental AAA is a common occurrence in in-hospital abdominal CTs. A significant number is not documented by the radiologist and the vast majority is not referred to monitoring. This could be a major reason for the low elective treatment rate of AAA in Portugal.

Although decreased protein kinase G (PKG) activity was proposed as potential therapeutic target in heart failure with preserved ejection fraction (HFpEF), randomized clinical trials (RCTs) with type-5 phosphodiesterase inhibitors (PDE5i) showed neutral results. Whether specific subgroups of HFpEF patients may benefit from PDE5i remains to be defined. Our aim was to test chronic sildenafil therapy in the young male ZSF1 obese rat model of HFpEF with severe hypertension and metabolic syndrome. Sixteen-week-old ZSF1 obese rats were randomly assigned to receive sildenafil 100 mg·Kg−1·d−1 dissolved in drinking water (ZSF1 Ob SIL, n = 8), or placebo (ZSF1 Ob PL, n = 8). A group of Wistar-Kyoto rats served as control (WKY, n = 8). Four weeks later animals underwent effort tests, glucose metabolism studies, hemodynamic evaluation, and samples were collected for aortic ring preparation, left ventricular (LV) myocardial adenosine triphosphate (ATP) quantification, immunoblotting and histology. ZSF1 Ob PL rats showed systemic hypertension, aortic stiffening, impaired LV relaxation and increased LV stiffness, with preserved ejection fraction and cardiac index. Their endurance capacity was decreased as assessed by maximum workload and peak oxygen consumption (V˙O2) and respiratory quotient were increased, denoting more reliance on anaerobic metabolism. Additionally, ATP levels were decreased. Chronic sildenafil treatment attenuated hypertension and decreased LV stiffness, modestly enhancing effort tolerance with a concomitant increase in peak, ATP levels and VASP phosphorylation. Chronic sildenafil therapy in this model of HFpEF of the young male with extensive and poorly controlled comorbidities has beneficial cardiovascular effects which support RCTs in HFpEF patient subgroups with similar features.

Introduction and objectives: In severe aortic stenosis (AS), the impact of aortic valve replacement (AVR) on left ventricular (LV) systolic function assessed by strain and measured by echocardiography or cardiac magnetic resonance (CMR) has been controversial. We aimed to investigate LV systolic myocardial function changes six months after AVR using global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain derived from CMR imaging. Methods: We included 39 severe AS patients (69.3±7.8 years; 61.5% male) with preserved LV ejection fraction (LVEF) who were recruited as part of the EPICHEART study and underwent successful AVR (aortic valvular area: 0.8 cm2 (IQR: 0.2) pre- to 1.8 cm2 (IQR:0.5) post-AVR). Structural and functional parameters were assessed at baseline and six months after AVR, including LV GRS, GCS and GLS analysis by CMR, using cine short-axial and two-, three-, and four-chamber long-axial view. Comparison between baseline and postoperative LV remodeling was performed using Student t-test and Wilcoxon test. Results: At six-month follow-up, LV mass, end-diastolic and end-systolic volumes, stroke volume, cardiac output, lateral E/e’, tricuspid annular plane systolic excursion, right ventricular (RV) S wave velocity, GLS [-15.6% (IQR: 4.39) to -13.7% (IQR: 4.62)] and GCS [-17.8±3.58% to -16.1±2.94%] reduced significantly, while LVEF and GRS remained unchanged and lateral e’ velocity increased. Conclusions: Despite favorable reverse LV structural and diastolic functional remodeling six months following AVR, GLS and GCS assessed by CMR reduced compared to baseline, LVEF remained unchanged. The clinical utility and timing of assessment of postoperative strain changes as a marker of systolic function progression needs further research. Resumo: Introdução e objetivos: Na estenose aórtica (EA), o impacto da substituição da válvula aórtica (SVA) na função sistólica do ventrículo esquerdo (VE), avaliado por strain medido por ecografia ou ressonância magnética cardíaca (RMC), ainda é controverso. Neste estudo, pretendemos investigar as alterações na função sistólica do VE seis meses após SVA, avaliadas por strain global longitudinal (SGL), circunferencial (SGC) e radial (SGR) medidos por RMC. Métodos: Foram incluídos 39 doentes com EA severa (69,3±7,8 anos; 61,5% sexo masculino) com fração de ejeção do VE (FEVE) preservada, recrutados no estudo EPICHEART, que foram submetidos a SVA bem-sucedida [área valvular aórtica (AVA): 0,8 cm2 (VIQ:0,2) pré-SVA para 1,8 cm2 (VIQ:0,5) pós-SVA]. Foram avaliados parâmetros de estrutura e função, incluindo SGL, SGC e SGR do VE por RMC, através da avaliação de imagens de eixo-curto e de eixo-longo de duas, três e quatro câmaras, antes e seis meses após SVA. Os valores pré e pós-operatórios da função e estrutura do VE foram comparados com o teste t de Student e com o teste de Wilcoxon. Resultados: Aos seis meses após SVA, verificou-se redução significativa da massa do VE, volumes telediastólico e telessistólico, volume de ejeção, débito cardíaco, rácio E/e’ lateral, TAPSE e onda S do ventrículo direito (VD), tal como do SGL [-15,6% (VIQ:4,39) para -13,7% (VIQ:4,62)] e do SGC [-17,8±3,58% para -16,1 ± 2,94%), enquanto a FEVE e o SGR não sofreram alterações significativas e a velocidade e’ aumentou. Conclusões: Apesar de uma remodelagem reversa estrutural e funcional diastólica favorável seis meses após SVA, o SGL e SGC medidos por RMC diminuíram e a FEVE não sofreu alterações significativas. A utilidade clínica e o tempo após intervenção para avaliar as alterações pós-operatórias do strain, como marcador de função sistólica, requerem investigação adicional.

Resumo Fundamento: Pouco se sabe sobre o impacto da estenose aórtica (EA) grave na rigidez aórtica e se ocorre alguma alteração após a remoção da barreira de EA com a cirurgia de substituição da válvula aórtica (SVA). Objetivo: Estimar as mudanças na velocidade de onda de pulso carotídeo-femoral (VOP) após a cirurgia de SVA e definir os preditores de VOP alta em pacientes com EA grave. Métodos: Estudo de coorte retrospectivo unicêntrico, incluindo pacientes com EA grave submetidos à cirurgia de SVA com bioprótese, entre fevereiro de 2017 e janeiro de 2019, e medições da VOP (Complior®) antes e depois do procedimento (2±1 meses). Antes e depois da SVA, os valores da VOP foram comparados por meio de testes pareados. foram analisadas as associações de VOP com dados clínicos, bem como aplicados modelos de regressão linear multivariada para estimar os preditores independentes da VOP pré- e pós-operatória. O nível de significância foi estabelecido em 5%. Resultados: Foram incluídos na amostra 150 pacientes, com média de idade de 72±8 anos, sendo 51% deles do sexo masculino. Identificamos um aumento estatisticamente significativo nos valores de VOP após a cirurgia (9,0 ± 2,1 m/s vs. 9,9 ± 2,2, p

Aims Assessing reversibility of pulmonary vascular changes through vasoreactivity testing (VRT) optimizes end‐stage heart failure patient selection for heart transplant. All efforts should be made to unload the left ventricle and reduce pulmonary vascular resistance to effectively exclude irreversible pulmonary hypertension. Methods and results We reviewed our centre's cardiac transplant registry database (2009–2017) for VRT and compared haemodynamic responses with 40 ppm inhaled NO (n = 14), 14–17 μg inhaled iloprost (n = 7), and 24 h 0.1 μg/kg/min intravenous levosimendan (n = 14). Response to levosimendan was assessed by repeat right heart catheterization within 72 h. Baseline clinical and haemodynamic features were similar between groups. VRT was well tolerated in all patients. All drugs effectively reduced pulmonary artery pressures and transpulmonary gradient while increasing cardiac index, although levosimendan had a greater impact on cardiac index increase (P = 0.036). Levosimendan was the only drug that reduced pulmonary artery wedge pressure (P = 0.004) and central venous pressures (P

Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology often associated with several comorbidities, such as left ventricle pressure overload, diabetes mellitus, obesity, and kidney disease. Its pathophysiology remains obscure mainly due to the complex phenotype induced by all these associated comorbidities and to the scarcity of animal models that adequately mimic HFpEF. Increased oxidative stress, inflammation, and endothelial dysfunction are currently accepted as key players in HFpEF pathophysiology. However, we have just started to unveil HFpEF complexity and the role of calcium handling, energetic metabolism, and mitochondrial function remain to clarify. Indeed, the enlightenment of such cellular and molecular mechanisms represents an opportunity to develop novel therapeutic approaches and thus to improve HFpEF treatment options. In the last decades, the number of research groups dedicated to studying HFpEF has increased, denoting the importance and the magnitude achieved by this syndrome. In the current technological and web world, the amount of information is overwhelming, driving us not only to compile the most relevant information about the theme but also to explore beyond the tip of the iceberg. Thus, this review aims to encompass the most recent knowledge related to HFpEF or HFpEF-associated comorbidities, focusing mainly on myocardial metabolism, oxidative stress, and energetic pathways.

Cardiovascular diseases (CVD) remain the biggest cause of deaths worldwide and a major socio-economic impact to society. In this work, we conducted an unbiased exploratory analysis of the large-scale lipidome in human plasma samples from patients with fatal and non-fatal CVD from large cohorts. The exploratory analysis included data from 10,349 individuals from 20 countries in Asia, Australasia, Europe and North America (ADVANCE cohort), and thus representative of the worldwide population. Through the analysis of hazard ratios (HR), we found 306 lipids relevant in CV Death and 294 lipids relevant in CV Events of which 262 lipids were common to fatal and non-fatal events followed over time (3, 5 and 8 years). Our exploratory analysis reveals that, over time, the plasma lipid signature found in non-fatal CVD events is similar to that preceding CVD death. Among the common lipid signature, we found that sphingolipids (HexCer, SM, Cer and other glycosphingolipids) and phospholipids (PC and PE) were strongly associated with CVD events outcome, while polyunsaturated plasmenyl PC and PE lipids were inversely associated with CV outcome. The restricted panel of specific lipids has the potential to improve CVD risk stratification and management, and significantly reduce the time involved in the analysis and data treatment in low-resolution MS instruments making plasma lipidomics a cost-efficient approach for clinical scenario. In our view, once standardized clinical, analytical and data reporting guidelines are implemented worldwide, lipid-based discriminators can be routinely applied in the CVD risk stratification and improve the performance of current clinical, biochemical and imaging diagnostic tools assisting the decision-making process particularly in patients with multiple co-morbidities.

Introduction: Accumulation of epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) and increased risk of coronary events in asymptomatic subjects and low-risk patients, suggesting that EAT promotes atherosclerosis in its early stage. Recent studies have shown that the presence of CAD affects the properties of adjacent EAT, leading to dynamic changes in the molecular players involved in the interplay between EAT and the coronary arteries over the history of the disease. The role of EAT in late-stage CAD has not been investigated. Objectives: In a comparative analysis with mediastinal and subcutaneous adipose tissue, we aim to investigate whether the volume of EAT assessed by computed tomography and its proteome assessed by SWATH-MS mass spectrometry are associated with late stages of CAD in an elderly cohort of severe aortic stenosis patients. Methods: The EPICHEART study (NCT03280433) is a prospective study enrolling patients with severe degenerative aortic stenosis referred for elective aortic valve replacement, whose protocol includes preoperative clinical, nutritional, echocardiographic, cardiac computed tomography and invasive coronary angiographic assessments. During cardiac surgery, samples of EAT and mediastinal and subcutaneous thoracic adipose tissue are collected for proteomics analysis by SWATH-MS. In addition, pericardial fluid and peripheral and coronary sinus blood samples are collected to identify circulating and local adipose tissue-derived biomarkers of CAD. Conclusion: We designed a translational study to explore the association of EAT quantity and quality with advanced CAD. We expect to identify new biochemical factors and biomarkers in the crosstalk between EAT and the coronary arteries that are involved in the pathogenesis of late coronary atherosclerosis, especially coronary calcification, which might be translated into new therapeutic targets and imaging tools by biomedical engineering. Resumo: Introdução: Acumulação de tecido adiposo epicárdico (TAE) tem sido associado a doença coronária aterosclerótica (DC) e aumento do risco de eventos coronários em indivíduos assintomáticos e doentes de baixo risco, sugerindo que o TAE pode promover fases precoces da DC. Estudo recentes mostraram que a presença de DC afeta as características do TAE adjacente levando a modificações dinâmicas nos mediadores envolvidos na comunicação entre o TAE e as artérias coronárias ao longo da história da DC. O papel doTAE nas fases avançadas da aterosclerose coronária não foi investigado. Objetivos: Através de análise comparativa com o tecido adiposo mediastínico e subcutâneo, pretendemos investigar se o volume do TAE, avaliado por tomografia computadorizada (TC), e o seu proteoma, avaliado por espectrometria de massa técnica de SWATH, estão associados a estadios avançados da DC numa coorte de estenose aórtica grave. Métodos: O estudo EPICHEART (NCT03280433) é um estudo prospetivo que inclui doentes com estenose aórtica grave referenciados para substituição eletiva da válvula aórtica, cujo protocolo envolve avaliação pré-operatória clínica, nutricional, ecocardiográfica, por TC e angiografia coronária invasiva. Durante a cirurgia cardíaca, colhemos amostras de tecido adiposo epicárdico, mediastínico e subcutâneo para análise do seu proteoma por espectrometria de massa técnica de SWATH. Adicionalmente, colhemos líquido pericárdico, sangue venoso periférico e do seio coronário para investigar mediadores de DC derivados do TAE na circulação sistémica e local. Conclusão: Desenhámos um estudo de translação para explorar a associação da quantidade e qualidade do TAE com a DC tardia. Esperamos identificar mediadores da comunicação recíproca entre o TAE e as artérias coronárias que estão envolvidos na patogénese das fases avançadas da DC, especialmente, calcificação coronária, os quais podem servir como novos alvos terapêuticos e soluções de engenharia biomédica para visualização da DC.

Prevalence of congenital heart diseases worldwide is around 9 per 1000 newborns, 20% of which affect the pulmonary valve or right ventricular outflow tract. As survival after surgical repair of these defects has improved over time, there is the need to address the long-term issues of older children and young adults with "repaired" congenital heart diseases. In recent decades, the most used types of valves are the mechanical and bioprosthetic valves. Despite improving patients' quality of life, these effects are suboptimal due to their limitations, such as the inability to grow and adapt to hemodynamic changes. These issues have led to the search for living valve solutions through tissue engineering to respond to these challenges. This article aims to review the performance of traditional pulmonary valves and understand how tissue engineering-based valves can improve the management of these patients.

INTRODUCTION The benefit of adding a second arterial conduit is still controversial, mainly in specific subgroups. We conducted a meta-analysis of randomized controlled trials (RCTs) and propensity score (PS) studies comparing survival and early results in elderly patients who underwent coronary artery bypass grafting (CABG) with multiple (MAG) versus single arterial grafting (SAG). EVIDENCE ACQUISITION MEDLINE, Web of Science and Cochrane Library were used to find relevant literature (1960-April 2020). Survival at a ≥ 1-year follow-up and early outcomes were evaluated. Outcomes were collected from matched samples or PS adjusted analysis: hazard ratio (HR) along with their variance, frequencies or odds ratios. Random effect models were used to compute combined statistical measures and 95% confidence intervals (CI) through generic inverse variance method (time-to-event) or Mantel-Haenszel method (binary events). EVIDENCE SYNTHESIS Eleven PS cohorts and 1 RCT comprising > 18,800 patients older than 70 (>6200 MAG and >12,500 SAG) were included in this meta-analysis. MAG was associated with lower long-term mortality (pooled HR: 0.81, 95%CI: 0.72-0.91, p

Background: Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Aortic valve replacement (AVR) is one of the most frequently performed cardiac surgeries, although there is scarce evidence on arrhythmic outcomes. We aimed to evaluate AF during the first year post- isolated aortic valve replacement surgery and its clinical, analytical, and echocardiographic predictors. Methods: Severe aortic stenosis patients with no prior atrial fibrillation submitted to isolated aortic valve replacement surgery were included in our study, of which 316 remained in sinus rhythm and 24 developed AF. We performed logistic regression searching for AF predictors and a longitudinal comparison between pre and post-operative echocardiographic data. Results: Postoperative AF (POAF), diabetes, and follow-up indexed Left Atrium Diameter (iLAD) were significantly higher in the group of patients developing AF. POAF and iLAD were independent AF predictors at follow-up. No differences between groups were found regarding baseline and follow-up echocardiographic data except for indexed Left Ventricle End-diastolic Diameter (LVED), which failed to decrease after surgery in the AF group. Conclusions: POAF and iLAD independently predicted AF at 1 year following isolated AVR surgery in aortic stenosis patients with no AF history. iLVED did not decrease significantly at follow-up in AF patients, possibly reflecting adverse ventricular remodeling.

Ruptured abdominal aortic aneurysm (rAAA) is a lethal condition that requires acute repair to prevent death. This analysis aims to assess the nationwide trends in rAAA admission, repair and mortality in a country, Portugal, without national screening for AAA.rAAA registered in the hospital administrative database of the National Health Service and all nationally registered deaths due to rAAA based on death certificate data were analysed. Three time periods (2000-2004, 2005-2009, and 2010-2015) were compared in patients ≥ 50 years old to assess the variations over time.A total of 2 275 patients ≥50 years old with rAAA were identified in the two databases from 2000 to 2015. The age standardised incidence of rAAA was 2.78 ± 0.24/100 000/year in 2000-2004, 3.17 ± 0.39/100 000/year in 2005-2009 and 3.21 ± 0.28/100 000/year in 2010-2015 (p .001). When comparing the time periods 2000-2004 to 2005-2009, the age standardised rate of admission (n = 1460) increased from 1.57 ± 0.25/100 000/year to 2.24 ± 0.32/100 000/year (p .001). The operative mortality rates decreased during this time period (from 55.3 ± 4.7% to 48.8 ± 4.7%, p .001). In 2010-2015, the age standardised rate of admissions due to rAAA decreased (1.98 ± 0.22/100 000/year). Operative mortality remained stable (48.9 ± 6.2%). The rate of patient deaths outside the hospital decreased from the first to the second period (1.21 ± 0.10/100 000/year and 0.93 ± 0.29/100 000/year, respectively) but later increased (1.14 ± 0.22/100 000/year). This resulted in a higher overall rAAA related mortality in Portugal in the third period (2.20 ± 0.18/100 000/year, 2.21 ± 0.27/100 000/year and 2.26 ± 0.26/100 000/year in 2000-2004, 2005-2009, and 2010-2015, respectively, p .001).Overall, the incidence of rAAA in Portugal has been stable over the past 10 years. The rates of admission, repair, and death due to rAAA repair seem to have reached an inflection point and are now decreasing. Mortality outside the hospital remains a matter of concern, warranting further planning of streamlined transfer networks and vascular surgical departments.

Septic cardiomyopathy is an increasingly relevant topic in clinical management of septic shock. However, pathophysiological mechanisms and long-term consequences of sepsis-induced myocardial injury are still poorly understood. Herein, new clinical and histological evidence is provided suggesting an association of myocardial edema formation with tissue injury and subsequent remodeling in septic shock patients. This preliminary data supports myocardial edema as a potentially relevant and largely unexplored mechanism of human septic cardiomyopathy.

Resumo Fundamento A aptidão física é um importante determinante da qualidade de vida (QV) em pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEP). No entanto, ainda não se sabe como os diferentes componentes da aptidão física se relacionam com as dimensões específicas da QV em pacientes com ICFEP. Objetivo Avaliar a associação entre diferentes componentes da aptidão física e dimensões da QV em pacientes com ICFEP, e examinar quais componentes da aptidão física foram independentemente associados à QV. Métodos Os pacientes com ICFEP foram avaliados quanto à aptidão física [equilíbrio dinâmico e mobilidade (“teste 8-feet Up-and-go ”), força da parte superior do corpo (Teste de força de preensão manual), aptidão cardiorrespiratória (ACR) (teste de caminhada de 6 minutos) e composição corporal (índice de massa corporal)] e para QV ( Minnesota Living With Heart Failure Questionnaire ). Uma correlação parcial foi utilizada para verificar a associação entre os componentes da aptidão física e as dimensões da QV. A análise das dimensões dos preditores independentes de QV foi realizada através da análise de regressão linear multivariada stepwise . A significância estatística foi estabelecida em p

Background/aims Heart failure with preserved ejection fraction (HFpEF) is recognised as an important cause of cardiovascular mortality and morbidity, accounting for approximately 50% of heart failure cases. Metabolic-related complications, such as obesity, have been associated with the pathophysiology of this complex syndrome. The anatomic proximity between cardiac visceral adipose tissue (CVAT) and the myocardium has been drawing attention due to its potential pathogenic role in cardiac diseases. Thus, we aimed to characterise the phenotypic and proteomic differences between CVAT from ZSF1 lean (control) and ZSF1 obese (HFpEF) rats as well as to evaluate the myocardial impact of conditioned media derived from CVAT of these 2 groups. Methods CVAT of 20-weeks-old lean and obese ZSF1 rats was collected for: 1) 24h DMEM incubation to obtain conditioned media, 2) separation of proteins to mass spectrometry identification, 3) adipokines' expression, 4) adipocytes cross-sectional area assessment. Organotypic cultures were prepared from 7 days-old Wistar Han cardiac explants and incubated for 24h with the conditioned media. After incubation, cross-section area of cardiomyocytes and fibrosis were evaluated. Cardiomyocytes were isolated from Wistar Han and incubated with conditioned media for viability studies. Results CVAT from lean rats presented a higher expression of uncoupling protein-1 (UCP-1) protein, associated with a multilocular appearance and an increased expression of brown adipose tissue markers. Contrarily, CVAT from obese rats revealed a white adipose tissue-like phenotype accompanied by hypertrophy of adipocytes. The analysis of the CVAT proteome reinforced the phenotypic differences between lean and obese CVAT, showing enrichment of proteins involved in triglyceride metabolic processes in obese CVAT. In contrast, mitochondrial proteins were prominent in lean CVAT, further suggesting a brown adipose tissue-like phenotype. The twenty-four hours-long incubation of myocardial organo-cultures with conditioned media obtained from CVAT obese (CM-obese) rats significantly reduced cell viability, induced cardiomyocytes hypertrophy and fibrosis, in stark contrast with the incubation with the conditioned media from lean rats CVAT (CM-lean). Furthermore, the deleterious effect imposed by CM-obese was associated with a pro-inflammatory profile, characterised by an increased expression of several pro-inflammatory adipokines. Conclusion Obesity promotes alterations in CVAT proteome signature, structure, composition and secretome, translating into dramatic myocardial consequences.

Aortic coarctation is a common congenital heart defect that often requires correction at a young age. Currently, success is defined by the achievement of a durable repair with low morbidity and mortality. We sought to systematically review the literature on risk factors for recoarctation and mortality in infants submitted to aortic arch coarctation repair under 1 year of age. PubMed and Scopus were searched for studies reporting risk factors for recoarctation and mortality from January 1989 to August 2019. Among the 1038 retrieved articles, 18 met the inclusion criteria, with a total of 2891 patients. The extracted risk factors for recoarctation were comprehensively summarized in the following categories: demographic variables, associated anomalies, clinical and repair variables, and morphometric variables. Younger age and lower weight were weak determinants of need for reintervention, while smaller aortic arch was a strong predictor of recoarctation. While balloon angioplasty is a clear risk factor for arch restenosis, the chosen surgical technique is not a strong risk factor. Associated minor cardiac anomalies and lower weight at surgery were important risk factors for death. Younger and smaller infants are at increased risk for adverse outcomes when submitted to aortic arch coarctation repair. This is particularly important when associated with smaller arch morphology. Strategies to improve the management of these patients may play a key role in improving their outcomes. Notably, surgical technique was not a strong predictor of recoarctation and mortality, suggesting that the choice of one over the other should be tailored.

The peptide hormone relaxin was originally linked to reproductive physiology, where it is believed to mediate systemic and renal hemodynamic adjustments to pregnancy. Recently, its broad range of effects in the cardiovascular system has been the focus of intensive research regarding its implications under pathological conditions and potential therapeutic potential. An understanding of the multitude of cardioprotective actions prompted the study of serelaxin, recombinant human relaxin-2, for the treatment of acute heart failure. Despite early promising results from phase II studies, recently revealed RELAX-AHF-2 outcomes were rather disappointing and the treatment for acute heart failure remains an unmet medical need. This article reviews the physiologic actions of relaxin on the cardiovascular system and its relevance in the pathophysiology of cardiovascular disease. We summarize the most updated clinical data and discuss future directions of serelaxin for the treatment of acute heart failure. This should encourage additional work to determine how can relaxin's beneficial effects be exploited for the treatment of cardiovascular disease.

Purpose: Postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) has been associated with increased risk of death in women but not in men. We aimed to explore predictors and long-term mortality in POAF following isolated aortic valve replacement (AVR) surgery in men and women. Methods: This study included 379 severe aortic stenosis patients with no prior atrial fibrillation (AF) who underwent isolated AVR surgery. We used multiple logistic regression to investigate independent gender-specific predictors of new-onset POAF, and we performed Kaplan–Meier (KM) to determine the impact of POAF in long-term mortality according to gender. Results: Advanced age and coronary artery disease prevalence were higher among POAF patients in both genders. On multiple analysis, increased postoperative peak lactate was independently associated with POAF in men, while lower mean aortic valve gradient was associated with POAF in women. Area under the curve (AUC) for the model was 0.77 [0.68–0.86] and 0.69 [0.60–0.78] for men and women, respectively. At 4-year follow-up, POAF was linked to increased risk of death in men but not in women. Conclusion: In severe aortic stenosis, factors associated with POAF and its impact on mortality differed between genders, with an increased risk of death observed only in men.

While guidelines for management of heart failure with reduced ejection fraction (HFrEF) are consensual and have led to improved survival, treatment options for heart failure with preserved ejection fraction (HFpEF) remain limited and aim primarily for symptom relief and improvement of quality of life. Due to the shortage of therapeutic options, several drugs have been investigated in multiple clinical trials. The majority of these trials have reported disappointing results and have suggested that HFpEF might not be as simply described by ejection fraction as previously though. In fact, HFpEF is a complex clinical syndrome with various comorbidities and overlapping distinct phenotypes that could benefit from personalized therapeutic approaches. This review summarizes the results from the most recent phase III clinical trials for HFpEF and the most promising drugs arising from phase II trials as well as the various challenges that are currently holding back the development of new pharmacotherapeutic options for these patients.

Introduction: Diastolic dysfunction is highly prevalent and a key pathophysiological contributor to several cardiovascular diseases, especially heart failure with preserved ejection fraction. In addition, some evidence suggests diastolic dysfunction is a risk factor for major adverse cardiovascular events. This study aimed to systematically review the evidence and to quantify the association between diastolic dysfunction and risk of cardiovascular events and death. Methods: MEDLINE was systematically searched from 1974 up to October 2017. We included cohort studies that assessed diastolic function in adults in the community, providing a definition of diastolic dysfunction regarding the occurrence of any cardiovascular event or mortality. For the quantitative analysis, relative risk estimates comparing individuals with versus without diastolic dysfunction were combined using a random effects model. Results: Nineteen studies were identified for inclusion in the systematic review, assessing a total of 63 802 participants. Nine studies were included in the meta-analysis. Diagnostic criteria and classification of diastolic dysfunction differed substantially between studies. The median prevalence of diastolic dysfunction in studies including individuals with and without diastolic dysfunction was 35.1% (range 5.3-65.2%). Comparing diastolic dysfunction with normal diastolic function, the summary relative risk estimate for cardiovascular events or mortality was 3.53 (95% CI: 2.75-4.53; I2=85.5%; nine studies). Conclusions: Although the definitions found in the literature differ, the diagnosis of diastolic dysfunction is associated with a 3.53-fold increased risk of cardiovascular events or death. This finding highlights the importance of developing easily applicable and consensual diagnostic criteria, as well as fostering research on effective treatment strategies when diastolic dysfunction is identified in the subclinical stage. Resumo: Introdução: A disfunção diastólica (DD) é muito prevalente e representa um mecanismo fisiopatológico central para várias doenças cardiovasculares, especialmente para a insuficiência cardíaca com fração de ejeção preservada. Além disso, alguns estudos sugerem que a DD se associa a um aumento do risco de eventos cardiovasculares. Este estudo pretende determinar se a DD é um preditor de eventos cardiovasculares e mortalidade através de uma revisão sistemática e meta-análise. Métodos: Foi realizada uma pesquisa na Medline, desde 1974 até outubro de 2017. Foram incluídos estudos de coorte que avaliassem a função diastólica em adultos da comunidade, comparando participantes com e sem DD, no que diz respeito ao desenvolvimento de eventos cardiovasculares ou morte. Na meta-análise, os riscos relativos foram combinados usando um modelo de random-effects analysis. Resultados: Foram identificados dezanove estudos para a revisão sistemática, avaliando um total de 63 802 participantes, dos quais nove foram incluídos na meta-análise. Observámos que os critérios de diagnóstico e classificação de DD foram bastante diferentes entre os estudos. A prevalência mediana de DD foi 35,1% (variabilidade 5,3%-65,2%). A presença de DD associou-se a um aumento significativo do risco relativo combinado de evento cardiovascular ou mortalidade (3,53; IC 95%: 2,75-4,53; I2=85,5%; 9 estudos). Conclusões: Apesar da heterogeneidade na definição de DD, a sua presença está associada a um aumento marcado do risco de eventos cardiovasculares ou morte. Este resultado realça a importância de desenvolver critérios objetivos e consensuais para o diagnóstico de DD, de modo a promover a sua identificação numa fase subclínica e eventualmente estimular uma investigação dirigida à abordagem terapêutica precoce. Keywords: Diastole, Myocardial relaxation, Diastolic dysfunction, Prognosis, Cardiovascular events, Heart failure, Palavras-chave: Diástole, Relaxamento miocárdico, Disfunção diastólica, Prognóstico, Eventos cardiovasculares, Insuficiência cardíaca

Aim Comparison of short and mid-term outcomes between off-pump CABG (OPCAB) and on-pump CABG (ONCAB) in patients older than 65 throughout a meta-analysis of randomized clinical trials (RCTs). Evidence acquisition A literature search was conducted using 3 databases. RCTs reporting mortality outcomes of OPCAB versus ONCAB among the elderly were included. Data on myocardial infarction, stroke, re-revascularization, renal failure and composite endpoints after CABG were also collected. Random effects models were used to compute statistical combined measures and 95% confidence intervals (CI). Evidence synthesis Five RCTs encompassing 6221 patients were included (3105 OPCAB and 3116 ONCAB). There were no significant differences on mid-term mortality (pooled HR: 1.02, 95%CI: 0.89-1.17, p=0.80) and composite endpoint incidence (pooled HR: 0.98, 95%CI: 0.88-1.09, p=0.72) between OPCAB and ONCAB. At 30-day, there were no differences in mortality, myocardial infarction, stroke and renal complications. The need for early re-revascularization was significantly higher in OPCAB (pooled OR: 3.22, 95%CI: 1.28-8.09, p=0.01), with a higher percentage of incomplete revascularization being reported for OPCAB in trials included in this pooled result (34% in OPCAB vs 29% in ONCAB, p Conclusions Data from RCTs in elderly patients showed that OPCAB and ONCAB provide similar mid-term results. OPCAB was associated with a higher risk of early rerevascularization. As CABG on the elderly is still insufficiently explored, further RCTs, specifically designed targeting this population, are needed to establish a better CABG strategy for these patients.

Background Post-operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Recent studies had shown this phenomenon is no longer considered transitory and is associated with higher risk of thromboembolic events or death. The aim of this study was to systematically review and analyze previous studies comparing oral anticoagulation therapy with no anticoagulation, regarding these long-term outcomes. Methods PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Database were systematically searched to identify the studies comparing the risk of stroke, or thromboembolic events or mortality of POAF patients who received anticoagulation compared with those who were not anticoagulated. Incidence of stroke, thromboembolic events and all-cause mortality were evaluated up to 10 years after surgery. Time-to-event outcomes were collected through hazard ratio (HR) along with their variance and the early endpoints using frequencies or odds ratio (OR). Random effect models were used to compute statistical combined measures and 95% confidence intervals (CI). Heterogeneity was evaluated through Q statistic-related measures of variance (Tau2, I2, Chi-squared test). Results Eight observational cohort studies were selected, including 15,335 patients (3492 on Oral Anticoagulants (OAC) vs 11,429 without OAC) that met the inclusion criteria for qualitative synthesis. Patients had a wide gender distribution (38.6–82.3%), each study with a mean age above 65 years (67.5–85). Vitamin K antagonists were commonly prescribed anticoagulants (74.3–100%). OAC was associated with a protective impact on all-cause mortality at a mean of 5.0 years of follow-up (HR is 0.85 [0.72–1.01]; p = 0.07; I2 = 48%). Thromboembolic events did not differ between the two treatment arms (HR 0.68 [0.40–1.15], p = 0.15). Conclusion Current literature suggests a possibly protective impact of OAC therapy for all-cause mortality in patients with new-onset atrial fibrillation after cardiac surgery. However, it does not appear to impact thromboembolism rate.