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The role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis.Relaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes.Relaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4-7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2-23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR.In chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

OBJECTIVE Patients with type 2 diabetes (T2D) have a high risk for developing heart failure (HF), which is associated with poor prognosis. Fenofibrate may reduce HF events through multiple mechanisms. We sought to study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the Action to Control Cardiovascular Risk in Diabetes lipid trial (ACCORD Lipid). RESEARCH DESIGN AND METHODS We used Cox regression analysis with background glucose-lowering strategy as the stratification variable. The median follow-up was 4.7 years. RESULTS A total of 5,518 patients were included. Median age was 62 years, and 31% were women. Prior HF history was present in 5% of the patients. The composite outcome of HF hospitalization or cardiovascular death occurred in 190 (6.9%) patients in the fenofibrate group vs. 228 (8.3%) in the placebo group: HR 0.82, 95% CI 0.68–1.00 (P = 0.048). The beneficial effect of fenofibrate to reduce HF hospitalizations or cardiovascular death was present among patients receiving standard glucose-lowering strategy, HR 0.64, 95% CI 0.48–0.85, and not among patients receiving intensive glucose-lowering strategy, HR 1.02, 95% CI 0.79–1.33 (Pinteraction = 0.017). A similar pattern was observed for HF hospitalizations alone. The effect of fenofibrate on blood lipids was not influenced by background glucose-lowering therapy in a clinically important manner. Fenofibrate caused more transient worsening estimated glomerular filtration rate (eGFR) events but slowed long-term eGFR decline. CONCLUSIONS In patients with T2D treated with simvastatin, fenofibrate reduced the composite of HF hospitalizations or cardiovascular mortality, an effect that was seen predominantly in patients with standard background glucose-lowering therapy.

Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER.Retrospective single-centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49-66] and 77% had paroxysmal AF. Median follow-up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p .001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99-7.35; p .001 and HR 2.73; 95% CI, 1.47-5.10; p = .002, respectively).The risk of LR after an index procedure of CA was significantly higher in patients with ER (five-fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period.

Background: It is particularly difficult to choose the appropriate prosthesis to treat infective endocarditis. Objectives: To investigate the outcomes after aortic valve replacement with a stented bioprosthesis (Trifecta) in patients with active or previous infective endocarditis. Methods: We performed a single-centre, retrospective study including consecutive patients with infective endocarditis who underwent aortic valve replacement between July 2011 and June 2019. Survival and reintervention were assessed as of December 2021. Hospital mortality was defined as death in-hospital or within 30-days of surgery. Kaplan-Meier method was used for time-to-event outcome assessment (all-cause mortality and reoperation). Data are median (minimum and maximum) or absolute (relative) frequencies. Results: We included 51 patients, median age of 69 (40 to 87) years, 78% male. The median follow-up time was 5.4 years and the maximum was 10 years. Most patients (71%) had native valve infective endocarditis and 16% had previous endocarditis. Surgery was urgent in 82%. Hospital mortality occurred in 10 patients (20%). After excluding these patients, 1-, 3-, 6-, and 9-years cumulative survival rates were 93%, 78%, 72%, and 72%, respectively. There were five bioprosthesis-related reoperations: 4 due to endocarditis at 1-year, 3-years, and 5-years on follow-up (n=1, 1 and 2, respectively) and 1 due to non-structural deterioration, 6-years after surgery. Conclusions: Despite the small sample size, this report supports a satisfactory performance profile of the Trifecta bioprosthesis in the treatment of infective endocarditis., Portuguese Journal of Cardiac Thoracic and Vascular Surgery, Vol. 29 No. 3 (2022): Jul - Sep

Previous studies have suggested that epicardial adipose tissue (EAT) could exert a paracrine effect in the myocardium. However, few studies have assessed its role in the risk of atrial fibrillation (AF) recurrence. This study aimed to evaluate the association between EAT volume, and its attenuation, with the risk of AF recurrence after AF ablation.A total of 350 consecutive patients who underwent AF ablation were included. The median age was 57 [IQR 48-65] years and 21% had persistent AF. Epicardial fat was quantified by multidetector computed tomography using Syngo.via Frontier-Cardiac Risk Assessment software, measuring pericardial fat volume (PATV), EAT volume, and attenuation of EAT posterior to the left atrium. AF recurrence was defined as any documented episode of AF, atrial flutter, or atrial tachycardia more than 3 months after the procedure.After a median follow-up of 34 [range, 12-57] months, 114 patients (33%) had AF recurrence. Univariable Cox regression showed that patients with an EAT volume ≥ 80 mL had an increased risk of AF recurrence (HR, 1.65; 95%CI, 1.14-2.39; P = .007). However, after multivariable adjustment, EAT volume did not remain an independent predictor of AF recurrence (HR, 1.24; 95%CI, 0.83-1.87; P = .3). Similar results were observed with PATV. Patients with lower attenuation of EAT did not have a higher risk of AF recurrence (log-rank test, P = .75).EAT parameters including the evaluation of EAT volume, PATV and EAT attenuation were not independent predictors of AF recurrence after catheter ablation.

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

The impact of "downstream" pathophysiological cardiac consequences in aortic regurgitation patients were not well established. The aim of our study was to validate a staging system built for severe aortic stenosis in a large real-world cohort of aortic regurgitation (AR) patients, evaluating the prevalence of different stages of cardiac damage and assess its prognostic impact. Clinical, echocardiographic and outcome data of patients with moderate-severe AR who underwent transthoracic echocardiography between January/2014 and September/2019 were retrospectively analysed. Patients were classified according to the extent of cardiac damage: Stage 0 (no cardiac damage), Stage 1 (left ventricular damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (tricuspid valve or pulmonary artery vasculature damage) and Stage 4 (right ventricular damage). The primary endpoint was all-cause mortality. A total of 571 patients (median age 73, 51% male) were enrolled: Stage 0 (14.0%), Stage 1 (21.5%), Stage 2 (49.2%), Stage 3 (12.3%) and Stage 4 (3.0%). Median follow-up time was 39.5 months (IQR 22.2 to 61.0). At the end of follow-up, cumulative death was significantly higher in more advanced disease stages (log-rank p 0.001). On multivariable analysis, Stage 3-4 was associated with increased risk of all-cause mortality (HR 3.20; 95% CI 1.48-6.93; p = 0.003). Our study suggests that extra-valvular damage is common in patients with significant AR and that a staging system developed for aortic stenosis also provides prognostic information in these patients. This staging system may be helpful for clinical decision-making regarding the time of valvular intervention.

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

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.

Introduction Pregnancy is a physiological condition of hemodynamic overload, characterized by a progressive reduction of peripheral vascular resistance, which normalizes postpartum. Purpose To characterize arterial stiffness and endothelial function during pregnancy and postpartum and to investigate the impact of cardiovascular (CV) risk factors. The secondary aim was to explore the potential association between pulse wave velocity (PWV) and risk for preeclampsia. Methods Prospective cohort study including volunteer pregnant women (healthy, obese and/or hypertensive) recruited in a tertiary centre between 2019 and 2020, at their 1st or 3rd trimester of pregnancy. Women were evaluated at the first trimester [10–15 weeks, baseline], third trimester [30–35 weeks, peak of CV remodelling] of pregnancy as well as at the 1st month and 6th month after delivery (CV reverse remodelling stages). The evaluation included clinical characterization through questionnaires as well as arterial stiffness and endothelial assessment by PWV and EndoPAT, respectively. Kruskal-Wallis H test and Friedman test were used as appropriate to between and within groups comparisons. Bonferroni correction was applied. Spearman correlation was performed to determine the relationship between PWV and risk for preeclampsia. Results We included 34 pregnant women with a median age of 34 [26; 41]years, 50% being hypertensive and/or obese. Arterial stiffness decreased significantly from the 1st to the 3rd trimester (6.3 [5.3 to 7.8] cm/s vs 5.6 [4.9 to 7.3] cm/s, p0.99). Compared to the healthy pregnant women, the CV risk factors group showed a higher pulse wave velocity only at the peak of CV remodelling (5.6 [5.3 to 7.3] cm/s vs 5.6 [4.9 to 7.2] cm/s, p=0.016), without any other differences in other parameters of time points evaluated. Pulse wave velocity at the first trimester revealed a positive association with risk for preeclampsia (r=0.485, p=0.026). Conclusion Our cohort presented a significant decrease in vascular resistance during pregnancy and normalization at the 6th month after delivery. Pregnant women with cardiovascular risk factors showed an increased arterial stiffness in the 3rd trimester compared to healthy pregnant women. Pulse wave velocity correlated positively with the risk for preeclampsia. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Universidade do Porto/FMUP and FSE-Fundo Social Europeu; FCT - Foundation for Science and Technology

Background The role and the indications for using off-pump coronary artery bypass surgery (OPCAB), instead of the traditional on-pump (ONCAB), is still to be addressed. Aim To describe our centre experience and to compare 15-years survival and early safety outcomes between OPCAB and ONCAB. Methods Single-centre retrospective cohort including 9-years of isolated first CABG (2005–2013). Multi-vessel disease with at least 2 surgical grafts patients were considered and the first 50 surgeries of each surgeon with each technique were excluded to account for the learning curve effect. Emergent surgeries and on-pump beating heart procedures were also excluded. A propensity-score matching (PSM) analysis was performed to balance groups and both survival and early outcomes comparison was done within the matched cohort using Kaplan-Meier or Cox stratified and paired tests, respectively. The median follow-up was 9 years, maximum 15 years. Results From 3012 multi-vessel patients with at least 2 surgical grafts, 2503 were included at the main analysis: 1487 ONCAB and 1016 OPCAB. ONCAB patients presented more frequently 3-vessels disease and left ventricular dysfunction, but received similar number of grafts than OPCAB, who in turn, received more frequently multiple arterial grafts. The surgical completeness of revascularization (CR) was similar, but hybrid procedures were more frequent in OPCAB raising CR rate in this group. After PSM (646 pairs), both groups were similar regarding pre and peri-operative characteristics. The long-term survival was similar (HR stratified by pair: 1.02 (0.81–1.30), but OPCAB evidenced benefits at early term results including bleeding, postoperative atrial fibrillation and stroke incidence. Conclusion At our centre, OPCAB performed by experienced surgeons provides rates of complete revascularization and long-term survival similar to ONCAB. In-hospital results favoured OPCAB. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Universidade do Porto/FMUP; Social European Fund; FCT-Fundação para a Ciência e a Tecnologia

Background The clinical associations and prognostic implications of the 6-minute walk test (6MWT) distance in patients with rheumatoid arthritis (RA) is yet to be explored. Aims To identify the clinical features and prognostic implications associated with the 6MWT in patients with RA. Methods Cohort study including 387 RA patients who underwent 6MWT. Regression models (linear and logistic) were built to identify independent predictors of shorter 6MWT distance. Cox proportional models were used to study the association of 6MWT distance with cardiovascular outcomes. Results Patients were subdivided according to 6MWT tertiles: 126 patients walked > 405m, 129 walked 345-405m, and 132 walked 55 year), elevated waist circumference, NT-pro BNP > 125pg/mL, anemia, C-reactive protein ≥ 3mg/dL, and troponin T ≥ 14pg/mL were independent predictors of walking shorter distances. Patients walking less than 345m had higher risk of a subsequent cardiovascular hospitalisation or cardiovascular death compared with patients walking 345m or more (adjusted HR: 2.98, 95%CI: 1.37–6.51, p = 0.006). Conclusions Older age, abdominal obesity, anemia, cardiac dysfunction, and inflammation were associated with walking shorter distances in patients with RA. Walking less than 345m in the 6MWT was associated with a poor cardiovascular prognosis. The 6MWT is simple, reproducible and inexpensive, easily performed in routine practice, and provides important information regarding the patients´ status and outcomes, enabling the monitorization of the therapeutic optimization of the various domains of the RA.

Background Patients with insulin-treated type 2 diabetes (T2D) have a high risk of major adverse cardiovascular events. Sodium-glucose cotransporter inhibitors (SGLTi) improve outcomes without hypoglycaemic risk. Aims To study the effect of SGLTi in patients with T2D with and without background insulin treatment in outcome-driven RCTs. Methods Random effects models. Results A total of 54 374 patients with T2D were included in the analysis, of which 26 551 (48.8%) were treated with insulin. For 3P-MACE in patients without insulin treatment, the HR (95% CI) for the effect of SGLTi vs placebo was 0.93 (0.81–1.05), with moderate heterogeneity (I2 = 49.2%, Q statistic P = 0.11). In insulin-treated patients, the HR (95% CI) was 0.88 (0.82–0.95), without evidence of heterogeneity (I2 =0.0%, Q statistic P =0.91). The pooled effect evidenced a 10% reduction of 3P-MACE with SGLTi (HR: 0.90, 95% CI: 0.85–0.96), without SGLTi-by-insulin interaction P = 0.53. For the composite outcome of HF hospitalisation or cardiovascular death in patients without insulin treatment, the HR (95% CI) for the effect of SGLTi vs placebo was 0.77 (0.61-0.92), with marked heterogeneity (I2 = 66.8%, Q statistic P = 0.02). In insulin-treated patients, the HR (95% CI) was 0.77 (0.68–0.86), without significant heterogeneity (I2 = 31.7%, Q statistic P = 0.25). The pooled effect evidenced a 23% reduction of HF hospitalisations or cardiovascular death with SGLTi (HR: 0.77, 95% CI: 0.68–0.85), without SGLTi-by-insulin interaction P = 0.98. Conclusion SGLTi reduces cardiovascular events regardless of insulin use. However, the treatment effect is more homogeneous among insulin-treated patients, supporting the use of SGLTi for the treatment of patients with T2D requiring insulin for glycaemic control.

Submitted by Gilson Rodrigues (gilson.rodrigues@ufvjm.edu.br) on 2022-08-22T16:57:46Z No. of bitstreams: 1 leila_francisca_saraiva_silva.pdf: 1915123 bytes, checksum: e92516db6a2702e0597b4d1c74e67229 (MD5) Approved for entry into archive by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2022-08-22T17:53:00Z (GMT) No. of bitstreams: 1 leila_francisca_saraiva_silva.pdf: 1915123 bytes, checksum: e92516db6a2702e0597b4d1c74e67229 (MD5) Made available in DSpace on 2022-08-22T17:53:00Z (GMT). No. of bitstreams: 1 leila_francisca_saraiva_silva.pdf: 1915123 bytes, checksum: e92516db6a2702e0597b4d1c74e67229 (MD5) Previous issue date: 2021 Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM) As institui??es financeiras possuem um papel importante para o desenvolvimento econ?mico do pa?s, pois elas det?m como principal pr?tica a media??o financeira, que consiste na utiliza??o de recursos de terceiros para executar suas atividades, isto ?, os recursos dos agentes econ?micos: fam?lias, institui??es p?blicas e privadas, s?o administrados por elas e isso exp?e a import?ncia de conhecer as principais fontes de receitas e os destinos dos lucros dessas institui??es. Diane disso, a presente pesquisa tem por objetivo identificar as origens dos lucros e seus destinos por meio da estrutura de controle acion?rio das institui??es financeiras cotadas na B3. Para atingir esse objetivo foi realizado uma pesquisa descritiva, bibliogr?fica e documental, de natureza qualitativa e quantitativa, cujo dados foram coletados na plataforma B3 e organizados em tabelas e quadros, divididos pelos segmentos de atua??o dessas empresas. Os resultados permitiram identificar que parte das institui??es tem como principal fonte de receitas provindas de suas atividades fins, enquanto que algumas utilizam as empresas como forma de investimento no mercado de valores mobili?rios, atrav?s de aplica??es financeiras, t?tulos e participa??es societ?rias. Quanto aos destinos dos lucros, constatou?se que a maior parte dos investidores diretos das institui??es estudadas s?o pessoas jur?dicas, cerca de 88%, elas foram identificas como empresas nacionais, internacionais, p?blicas, grupos econ?micos e outros, e quanto aos investidores indiretos finais, 33% das institui??es estudadas tem seu controle acion?rio familiar, ou seja, quando uma ou mais fam?lias comandam a empresa atrav?s das a??es ordin?rias. Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Tecnologia, Ambiente e Sociedade, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2021. Financial institutions play an important role in the country's economic development, as they have as their main practice financial mediation, which consists of using third?party resources to carry out their activities, that is, the resources of economic agents: families, public and private institutions, are managed by them and this exposes the importance of knowing the main sources of revenue and the destinations of profits of these institutions. Therefore, this research aims to identify the origins of profits and their destinations through the shareholding structure of financial institutions listed on B3. To achieve this objective, a descriptive, bibliographical and documentary research was carried out, of a qualitative and quantitative nature, whose data were collected on platform B3 and organized into tables and charts, divided by the segments in which these companies operate. The results allowed us to identify which part of the institutions have as their main source of income from their main activities, while some use companies as a form of investment in the securities market, through financial investments, bonds and equity interests. As for the destinations of profits, it was found that most of the direct investors of the institutions studied are legal entities, about 88%, they were identified as national, international, public companies, economic groups and others, and as for the final indirect investors, 33% of the institutions studied have their family shareholding control, that is, when one or more families command the company through common shares.

Background and aim The use of more than one arterial conduit in coronary surgery has been widely associated with better long-term results. We sought to investigate the benefits of Multiple Arterial Grafts (MAG) over Single Arterial Grafts (SAG), among diabetic patients, in short and long-term results throughout a meta-analysis of propensity score matching (PSM) studies. Methods MEDLINE and ISI Web of Science were used to find relevant literature (1960–2018). We included cohort studies with at least 200 patients and that reported one of these outcomes: long-term survival, early mortality or sternal wound infection (SWI). Survival was collected through hazard ratio (HR) along with their variance and the other endpoints using frequencies or odds ratio (OR) from the matched sample. Fixed effect models were used to compute statistical combined measures and 95% confidence intervals (CI). Results Eleven studies were included performing a total of 9670 diabetic patients: 4833 MAG and 4837 SAG (1:1 PSM in all studies). MAG group consisted in bilateral internal mammary artery (BIMA) in 8 studies; single IMA (SIMA)+radial artery (RA) in 5 studies; and one study reported several MAG approaches: BIMA+RA+Gastroepiploic artery (GEA), SIMA+RA+GEA, SIMA+GEA or BIMA+GEA. SAG group consisted in SIMA with or without saphenous vein graft in all studies, except for one that included also patients with GEA instead of SIMA. Ten studies reported long-term survival and mean follow-up time ranged from 5 to 12 years (max. follow-up 30y). Overall, MAG had significantly improved long-term survival compared with SAG (pooled HR=0.79, 95% CI: 0.74–0.85, p Conclusion Considering PSM studies, MAG provides superior long-term survival compared to SAG in diabetic patients. This surgical technique does not implement additional risk regarding in-hospital mortality, but MAG with BIMA was associated with a higher risk of SWI in this specific subgroup of patients. Forest plot survival Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Universidade do Porto/FMUP e FSE-Fundo Social Europeu, NORTE 2020-Programa Operacional Regional do Norte,-Programas Doutorais

Background There is currently conflicting evidence regarding the security profile and outcomes of dual antiplatelet therapy (DAPT) in patients following coronary artery bypass grafting (CABG). Aim We aim to compare the effect of early DAPT in short and long-term survival versus acetylsalicylic acid in a monotherapy regimen (ASA). Therapy's safety was evaluated through immediate or early postoperative outcomes, with particular emphasis on the haemorrhagic. Methods Single-centre retrospective cohort study on consecutive patients undergoing 1st isolated CABG surgery in 2010. Median follow-up time was 9 years. Pre-, peri- and postoperative data was collected through clinical files and digital databases. The DAPT and ASA groups were defined considering the administration of clopidogrel plus acetylsalicylic acid and only acetylsalicylic acid, respectively, within a 24h window after CABG. T-tests and Pearson's chi-squared tests were used for group comparison. Survival analysis was performed using Kaplan-Meier curves, Log-Rank test and multivariable Cox regression. Propensity scores (PS) were estimated using a multivariable logistic regression model and included in multivariable regressions as a covariate along with DAPT. Early mortality was defined if occurred before discharge or within the 30 days following the surgery; bleeding was assessed through red blood cells' (RBC) transfusion, re-exploration of thorax and drainage. Results We included 351 patients, 81% were male, and DAPT was performed in 251 patients (72%). DAPT patients were younger (63±10 vs. 66±10 years, p=0.007) but both groups were similar regarding the cardiovascular modifiable risk factors. Kaplan-Meier curves showed similar cumulative survival between groups (75% in DAPT vs. 67% in ASA group, at 9 years of follow-up, Log-rank p=0.103), as well as the PS adjusted analysis (HR DAPT: 0.93, 95% CI: 0.57–1.51). Regarding safety outcomes, we found no differences in early mortality (two cases in the DAPT group and one in the ASA group). Total median cell-saver transfusion (300mL vs. 250mL, p=0.318) and the re-exploration of thorax due to bleeding (1.6% vs. 4% p=0.231) showed no statistical significance either. On the other hand, post-operative total median chest tube drainage was higher in the ASA group (1220mL in DAPT vs. 1300mL in ASA, p=0.043). There was also a lower frequency of DAPT patients requiring 3 or more peri and postoperative RBC transfusions (8.5% vs. 13.3% p Conclusion Compared with ASA, DAPT showed a non-significant impact on long-term survival but demonstrated to be a safe option within the assessed bleeding outcomes. Further studies are needed to provide recommendations on the therapeutical strategy following CABG. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Universidade do Porto/FMUP, FSE-Fundo Social Europeu, NORTE 2020-Programa Operacional Regional do Norte, Programas Doutorais. Project NetDIAMOND, supported by ESIF under Lisbon Portugal Regional Operational Programme and National Funds through FCT

International audience; Patients with rheumatoid arthritis (RA) are at higher risk for having underdiagnosed heart failure, however there are no recommendations regarding echocardiographic screening. We aimed to determine the prevalence of subclinical ventricular dysfunction in RA applying current echocardiographic guidelines, its association with patients' characteristics, biomarkers and prognostic parameters and compare the 2016 guidelines to the recommendations from 2009. Prospective study of RA patients without known heart disease, categorized as preserved ventricular function (PVF), systolic dysfunction (SD), isolated diastolic dysfunction (DD) or indeterminate diastolic function (IDF) as per the 2016 echocardiography guidelines-or any ventricular dysfunction (AVD) comprehending the last 3. The median age was 58 years and 78% were females. The majority had PVF (73%), followed by DD (13%), IDF (11%) and SD (4%). Concordance with the 2009 echocardiographic guidelines was low. Compared with PVF, AVD patients were older (65 vs 55 years, p 57 years) was the only independent predictor of AVD or DD. AVD was significantly associated with higher NT-proBNP and lower distance in 6-min walk test. There were no significant independent associations between characteristics of RA disease and ventricular function. A total of 17% of RA patients without known cardiovascular disease presented subclinical systolic or diastolic dysfunction, which was associated with older age. The echocardiographic screening may have clinical value in identifying subclinical ventricular dysfunction, especially in older RA patients.

Background Rheumatoid arthritis (RA) patients have high risk of heart failure (HF). Aims Identifying the risk factors and mechanistic pathways associated with HF in patients with RA. Methods Cohort study enrolling 355 RA patients. HF was defined according to the ESC criteria. 93 circulating protein-biomarkers (91CVDIIOlink®+troponin-T+c-reactive protein) were measured. Regression modeling (multivariate and multivariable) were built and network analyses were performed - based on the identified relevant protein biomarkers. Results 115 (32.4%) patients fulfilled the ESC criteria for HF, but only 24 (6.8%) had a prior HF diagnosis. Patients with HF were older (67 vs. 55yr), had a longer RA duration (10 vs. 14yr), had more frequently diabetes, hypertension, obesity, dyslipidemia, atrial fibrillation, and ischemic arterial disease. Several protein-biomarkers remained independently associated with HF, the top (FDR1%) were adrenomedullin, placenta-growth-factor, TNF-receptor-11A, and angiotensin-converting-enzyme-2. The networks underlying the expression of these biomarkers pointed towards congestion, apoptosis, inflammation, immune system signaling and RAAS activation as central determinants of HF in RA. Similar HF-associated biomarker-pathways were externally found in patients without RA. Having RA plus HF increased the risk of cardiovascular events compared to RA patients without RF; adjusted-HR (95%CI)=2.37 (1.07-5.30), p=0.034 Conclusion Age, cardiovascular risk factors, and RA duration increase the HF odds in patients with RA. Few RA patients had a correct prior HF diagnosis, but the presence of HF increased the patients` risk. RA patients with HF largely share the mechanistic pathways of HF patients without RA. Randomized HF trials should include patients with RA. ClinicalTrials.gov ID NCT03960515

Objectives: We conducted a meta-analysis of randomized controlled trials (RCTs) and propensity score (PS) studies comparing survival and major adverse cardiac and cerebrovascular events (MACCEs) of patients who underwent coronary artery bypass grafting (CABG) with multiple (MAG) versus single arterial grafting (SAG). Methods: MEDLINE, Web of Science and Cochrane Library were used to find relevant literature (1960-2018). Survival at a follow-up ≥ 1 year, MACCEs and early outcomes were evaluated. Time-to-event outcomes were collected through hazard ratio (HR) along with their variance, and the other endpoints using frequencies from matched sample or adjusted 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). Results: Twenty-nine PS cohorts and 8 RCTs comprising 122832 patients (52178 MAG and 70654 SAG) were included in this meta-analysis. MAG was associated with lower early mortality (OR: 0.82, 95%CI: 0.71-0.95, p=0.007), long-term mortality (HR: 0.76, 95%CI: 0.73-0.78, p

INTRODUCAO: A evidencia existente relativamente aos outcomes da terapia de dupla antiagregacao (DAPT) em pacientes submetidos a cirurgia de revascularizacao do miocardio (CABG) e conflituosa. Com este estudo, pretendemos comparar outcomes de sobrevivencia e seguranca da DAPT versus aspirina (ASA) numa janela temporal de 24h apos CABG. METODOS: Estudo unicentrico de coorte retrospetiva, em pacientes submetidos consecutivamente a primeiro CABG isolado em 2010. A analise de sobrevivencia (mediana de follow-up de 9 anos) foi realizada com curvas Kaplan-Meier e regressao multivariada Cox utilizando Propensity Score (PS) como covariavel com DAPT. A hemorragia foi avaliada atraves da transfusao de globulos rubros (RBC), re-exploracao do torax e drenagem pos-operatoria. RESULTADOS: Incluimos 351 pacientes, 251 dos quais sob DAPT (71.5%). As curvas Kaplan-Meier demonstram sobrevivencia cumulativa similar entre grupos (9a: 75% DAPT vs. 67% ASA, Log-rank p=0.103), bem como na analise ajustada por PS (HR DAPT: 0.93, 95%CI:0.57-1.51). Tendo em conta outcomes de seguranca, nao encontramos diferencas na mortalidade precoce (2 no grupo DAPT e 1 no grupo ASA). A transfusao mediana total do cell-saver (300mL vs. 250mL, p=0.318) e a re-exploracao do torax devido a hemorragia (1.6% vs. 4%, p=0.231) tambem nao mostra diferenca estatisticamente significativa. Por outro lado, a drenagem toracica pos-operatoria foi superior no grupo ASA (1220mL DAPT vs. 1300mL ASA, p=0.043). Tambem verificamos, nos pacientes DAPT, uma necessidade inferior de ≥3 transfusoes RBC no peri e pos-operatorio (8.5% vs. 13.3% p

Objective: To report the hemodynamic profile and short- and medium-term outcomes of Freedom Solo and Solo Smart stentless aortic valves implanted at our center. Methods: Between 2009 and 2015, all patients undergoing aortic valve replacement using Solo stentless valves at our center were enrolled. Clinical and echocardiographic follow-up was carried out six months postoperatively. Survival and major events, including structural valve deterioration and non-structural valve dysfunction, endocarditis, reoperation and stroke, were assessed through medical records or telephone interview with the referring cardiologist up to November 2015 (mean and maximum follow-up 39±22 and 78 months, respectively). Results: Patients’ (n=345) mean age was 72±8 years, 52% were female and median euroSCORE II was 2.7 (1.5-4.7). There was no intraoperative mortality and in-hospital mortality was 2.6%. Postoperatively, mean transvalvular gradient was 11.9±4.5 mmHg and effective orifice area was 1.9±0.5 cm2. Patient-prosthesis mismatch occurred in 14% but was severe in only one patient. Cumulative survival at six years was 72%. Six patients were reoperated: three due to endocarditis, two for structural prosthesis deterioration and one because of periprosthetic fistula. Five patients suffered stroke, three had medically-treated endocarditis and one had structural valve deterioration but was not considered suitable for reoperation. None of the remainder had structural valve deterioration or non-structural valve dysfunction. Conclusions: Solo stentless aortic valves are safe to implant, with promising clinical outcomes in short- and medium-term assessment. Moreover, they show an excellent hemodynamic performance: low transvalvular gradients, large effective orifice areas and low incidence of patient-prosthesis mismatch. Resumo: Objetivo: Descrever o perfil hemodinâmico e resultados clínicos a curto e médio prazo das biopróteses aórticas stentless Freedom SOLO e SOLO Smart implantadas no nosso Centro. Métodos: Foram incluídos todos os doentes submetidos a substituição valvular aórtica por biopróteses stentless SOLO no nosso Centro, entre 2009 e 2015. O follow-up clínico e ecocardiográfico foi aos seis meses de pós-operatório. A sobrevida e eventos major (deterioração valvular estrutural, disfunção valvular não estrutural, endocardite, reoperação, acidente vascular cerebral) foram aferidos através de registos clínicos e entrevista telefónica com o Cardiologista assistente até novembro de 2015 (follow-up médio 39±22 meses, máximo 78). Resultados: A idade média dos doentes (n=345) foi 72±8 anos, 52% eram do sexo feminino e a mediana de euroSCORE II foi 2,7 (1,5–4,7). A mortalidade hospitalar foi 2,6%, não havendo mortalidade intra-operatória. O gradiente transvalvular médio pós-operatório e a média da área de orifício efetivo foram 11,9 ±4,5 mmHg e 1,9 ±0,5 cm2, respetivamente. O mismatch prótese-doente ocorreu em 14% dos casos, sendo um severo. A sobrevida cumulativa aos seis anos foi 72%. Seis indivíduos foram reoperados: três por endocardite infeciosa, dois por deterioração protésica e um por fístula periprotésica. Registaram-se cinco acidentes vasculares cerebrais, três endocardites tratadas farmacologicamente e um caso de deterioração valvular sem condições clínicas para reoperação. Não se registaram outras deteriorações valvulares estruturais ou disfunções valvulares não estruturais. Conclusões: As biopróteses stentless SOLO apresentaram resultados a curto e médio prazo promissores, revelando um excelente perfil hemodinâmico: baixos gradientes transvalvulares, áreas de orifício efetivo grandes e baixa incidência de mismatch prótese-doente. Keywords: Aortic valve replacement, Stentless aortic bioprosthesis, Cardiac surgery, Palavras-chave: Substituição valvular aórtica, Bioprótese aórtica stentless, Cirurgia cardíaca

Objectives The goal of this study was to compare the stentless Freedom Solo® (FS) and the stented Trifecta® (TF) aortic bioprostheses with regard to haemodynamic profile, left ventricular mass regression and early and late postoperative outcomes and survival. Methods A longitudinal cohort study of consecutive patients undergoing aortic valve replacement (2009-16) with either the FS or TF at 1 centre was performed. Local databases and national records were queried. Prosthesis haemodynamics and left ventricular dimensions were obtained from postoperative echocardiograms. After propensity score matching (21 covariates), the Kaplan-Meier and competing risk analyses were performed for survival and the combined outcome of structural valve deterioration and endocarditis, respectively. Haemodynamics and mass regression were assessed by a mixed-effects model including propensity score as a covariate. Results From a total sample of 397 patients with the FS and 525 TF bioprostheses with a median follow-up time of 4.0 (2.2-6.0) and 2.4 (1.4-3.7) years, respectively, a matched sample of 329 pairs was obtained. Matched groups showed no differences in survival (hazard ratio = 1.04, 95% confidence interval = 0.69-1.56) or cumulative hazards of combined outcome (subdistribution hazard ratio = 0.54, 95% confidence interval = 0.21-1.39). Although the TF showed an improved haemodynamic profile, no difference was found in mass regression. Patients with TF bioprostheses had higher rates of prolonged mechanical ventilation, whereas patients with the FS bioprosthesis showed higher rates of thrombocytopenia. Conclusions The TF showed an improved haemodynamic profile compared to the FS, but this did not translate into further reverse remodelling. Postoperative outcomes and survival rates were comparable for both bioprostheses. Long-term follow-up is needed for comparisons with classical bioprosthesis models.

Currently, aortic valve replacement is the only treatment capable of relieving left ventricle pressure overload in patients with severe aortic stenosis. It aims to improve cardiac function and revert hypertrophy, by triggering myocardial reverse remodeling. Despite immediately relieving afterload, reverse remodeling turns out to be extremely variable. Among other factors, the extent of reverse remodeling may depend on how well ubiquitin-proteasome system tackle hypertrophy. Therefore, we assessed tagged ubiquitin and ubiquitin ligases in the left ventricle collected from patients undergoing valve replacement and tested their association to the degree of reverse remodeling. Patients were classified according to the regression of left ventricle mass (ΔLVM) and assigned to complete (ΔLVM≥15%) or incomplete (ΔLVM≤5%) reverse remodeling groups. No direct inter-group differences were observed. Nevertheless, correlation analysis supports a fundamental role of the ubiquitin-proteasome system during reverse remodeling. Indeed, total protein ubiquitination was associated to hypertrophic indexes such as interventricular septal thickness (r = 0.55, p = 0.03) and posterior wall thickness (r = 0.65, p = 0.009). No significant correlations were observed for Muscle Ring Finger 3. Surprisingly, though, higher levels of atrogin-1 were associated to postoperative interventricular septal thickness (r = 0.71, p = 0.005). In turn, Muscle Ring Finger 1 correlated negatively with this postoperative hypertrophy marker (r = -0.68, p = 0.005), suggesting a cardioprotective role during reverse remodeling. No significant correlations were found with left ventricle mass regression, although a trend for a negative association between the ligase Murine Double Minute 2 and mass regression (r = -0.44, p = 0.10) was found. Animal studies will be necessary to understand whether this ligase is protective or detrimental. Herein, we show, for the first time, an association between the preoperative myocardial levels of ubiquitin ligases and postoperative hypertrophy, highlighting the therapeutic potential of targeting ubiquitin ligases in incomplete reverse remodeling. CC BY 4.0

Background Considering selected patients and the expertise of the surgical team, aortic valve repair (REPAIR) has been recognized as an alternative to aortic valve replacement. Aim To compare mid-term survival, need of reoperation and hemodynamic results after mechanical replacement (MECH) or REPAIR in non-stenotic aortic valve disease. Methods Retrospective single-center cohort study including consecutive patients younger than 70 years-old, with non-stenotic aortic valve disease, who underwent 1st aortic valve surgery with MECH or REPAIR (2 experienced surgeons), during a 6-year period. Concomitant procedures were not excluded. First follow-up echocardiogram was performed within 3 months after surgery (median). Mean follow-up time was 4 years, maximum 7. According to the data distribution appropriate statistical tests to compare independent samples were used. Mid-term survival and need of reoperation were studied through Kaplan-Meier curves and Cox regression. Results MECH was performed in 94 (56.6%) and REPAIR in 72 patients. Individuals in MECH group were older and presented higher NYHA functional class than REPAIR group (51±11 vs 47±13 years, p=0.048; 30 vs 4%, p Conclusion Aortic valve repair seems to be safe and effective in this single-center study showing similar results comparing with mechanical aortic valve replacement. We should reinforce the need of judiciously select patients for this complex surgical technique and the specialized training of the surgical team. Further studies are needed to provide reliable recommendations on this theme.

Introduction Coarctation of the aorta (CoA) is characterized by diffuse arteriopathy which can persist to upward of the aortic isthmus, even after successful surgical correction. This arteriopathy can also occur in the pulmonary vasculature, leading to pulmonary hypertension (PH), a strong risk factor of poor prognosis in CoA population. Purpose The purpose of this study was to determine the incidence of systemic and pulmonary hypertension in a CoA paediatric population after surgical repair, as well as the impact of PH in right ventricular function. Methods This cross-sectional study included children after successful surgical repair of the CoA in a tertiary centre [1996, 2009] up to the first year of age. Children with other cardiac structural lesions or recoarctation were excluded. Systemic arterial hypertension was defined as blood pressure in the 95th percentile or higher. PH was considered if the estimated pulmonary systolic arterial pressure (PSAP) was higher than 30mmHg. Pulse wave velocity, ambulatory 24 hours blood pressure monitoring, echocardiographic assessment of right ventricle (RV) and blood tests were performed 11±4 years after surgical procedure. Echocardiographic variables were normalized and evaluated by z-scores. One sample t test or sign test was used to estimate the deviation of measured/observed values from the normality/expected values (defined by z-score=0). Results We included 38 children with a mean age of 12±4 years (63% male). Late arterial hypertension was diagnosed in 29% of the children and PH incidence was 68% with a mean PSAP of 37±5mmHg. The mean of A' wave (z-score: 0.34±0.93, p=0.030) and median of E/E' ratio (z-score: 0.46 [−1.32; 3.68], p=0.004) z-scores were increased comparing with expected normal values in paediatric population. Moreover, E' wave (z-score: −0.35±0.98, p=0.034) and RV index of myocardial performance (z-score: −0.20±0.41, p=0.006) were decreased. Regarding RV systolic function, TAPSE z-score was significantly increased (z-score: 2.06±2.33, p Conclusion Children submitted to CoA surgical repair before the first year of life showed a higher PH incidence than late systemic hypertension occurrence. Also, they already present with significant RV functional abnormalities when compared to the normal paediatric population. These abnormalities can underlie pulmonary vascular remodelling after left ventricular pressure overload in CoA population that seems irreversible after pressure overload relief. Acknowledgement/Funding AFF are supported by FCT (SFRH/BD/138925/2018)