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BACKGROUND Patients with acute severe aortic regurgitation (AR) due to infective endocarditis can progress rapidly from the hemodynamically stable patient to pulmonary edema and cardiogenic shock. We sought to identify patients at risk of decompensation where emergent surgery should be undertaken. METHODS We identified 90 patients with acute severe AR from the echocardiography laboratory database. Baseline clinical, hemodynamic (heart rate (HR) and blood pressure (BP)), and echocardiographic data including mitral filling, premature mitral valve closure (PMVC), and diastolic mitral regurgitation (DMR) were identified. The primary endpoint was subsequent development of pulmonary edema or severe hemodynamic instability. RESULTS Patients who met the primary endpoint had a higher HR (98.5 bpm vs 80.5 bpm), lower diastolic BP (54 mm Hg vs 61.5 mm Hg), higher mitral E-wave velocity (113 cm/s vs 83 cm/s), higher E/e' ratio (12.4 vs 8), higher proportion of DMR (27.8% vs 7.4%), and PMVC (25% vs 9.3%) than patients who did not meet the endpoint. The proportion of patients with the primary endpoint increased as HR increased ((≤81 bpm) 3/30 (10%), (81-94 bpm) 11/31 (35.5%), (≥94 bpm) 22/29 (75.9%), P

The outcome of secondary mitral regurgitation (MR) in patients with heart failure is poor. Survival is related to the severity of MR. We sought to investigate the effect of left ventricular contractility, the ratio of left ventricular end-diastolic volume (LVEDV) to effective orifice area (EROA) and the ratio of regurgitant volume (RVol) to stroke volume (SV) on cardiovascular survival.188 patients with a left ventricular ejection fraction (LVEF) 50% and secondary MR were included. Groups were divided into tertiles. The Kaplan Meier method and log rank test were used to identify differences in survival between groups. Cox regression was used to identify independent predictors of cardiac mortality.Median follow-up was 30.4 months. Patients with a more abnormal global longitudinal strain (GLS) had lower survival, p = 0.001. There was no difference in survival between patients with an LVEF30%, 30%-40% and 40%, p = 0.27. Patients with a higher RVol/SV ratio had lower survival than those with a lower ratio, p 0.0001. Patients with a lower LVEDV/EROA ratio had worse survival than those with a higher ratio, p 0.0001. Independent predictors of cardiovascular mortality were GLS (5.6%) hazard ratio (HR) 2.7, the ratio of RVol/SV (1.38) HR 4.96 and the ratio of LVDEV to EROA (263) HR 4.49.The main determinants of cardiovascular mortality in patients with secondary MR and heart failure are more abnormal GLS, lower LVEDV/EROA ratio and higher RVol/SV ratio. These may help risk stratify patients to help determine the optimal management strategy.

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive “cross-talk” with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2). Introduction: Our study is an “in situ” morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored. The aim of the present study was to determine the role of ERβ and NFAT in the underlying pathophysiology of obesity and related comorbidities. We have investigated the expression of specific proteins using immunochemistry methodologies. Methods: Our population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver and the differential protein expression was evaluated by immunohistochemistry. Results: We demonstrated an extensive intra- and inter-tissue co-expression network, which confirms the tissue-specific and integral role of each one of the investigated proteins in morbid obesity. Moreover, a beneficial role of ERβ and NFATc1 against NAFLD is implicated, whereas the distinct roles of TIF2 still remain an enigma. Conclusions: We believe that our findings will shed light on the complex underlying mechanisms and that the investigated biomarkers could represent future targets for the prevention and therapy of obesity and its comorbidities.

Background: Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function. Objective: We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation. Methods: This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post-ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI

Background: Obesity is a global epidemic which is associated with several cardiometabolic comorbidities and is characterized by chronic, low grade systemic inflammation. Numerous biomarkers have been implicated in the pathophysiology of the disease, including transcription factors and coregulators. Steroid Receptor Coactivator (SRC)-family represent the master regulators of metabolic pathways and their dysregulation is strongly associated with numerous metabolic disorders. Methods: 50 morbidly obese patients participated in the present study. Biopsies were collected from visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, extra-myocellular adipose tissue and liver. We evaluated the differential protein expression of NFATc1, SRC-2/TIF-2, SRC-3/AIB-1 and inflammatory biomarkers CD68 and CD3 by immunohistochemistry. The current study was designed to determine any correlations between the transcription factor NFATc1 and the SRC coregulators, as well as any associations with the inflammatory biomarkers. Results: We identified SRC-3 as a hepatic NFATc1 coactivator and we demonstrated its possible role in energy homeostasis and lipid metabolism. Moreover, we revealed a complex and extensive intraand inter-tissue network among the three main investigated proteins and the inflammatory biomarkers, suggesting their potential participation in the obesity-induced inflammatory cascade. Conclusions: Steroid receptor coactivators are critical regulators of human metabolism with pleiotropic and tissue-specific actions. We believe that our study will contribute to the better understanding of the complex multi-tissue interactions that are disrupted in obesity and can therefore lead to numerous cardiometabolic diseases. Further on, our present findings suggest that SRC-3/AIB-1 could constitute possible future drug targets.

(1) Background: A great number of inflammatory mediators and metabolic biomarkers have been shown to contribute to the development and progression of obesity-induced pathologies, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). Many of those mediators are either targets or activators of nuclear factor-κappa B (NF-κB), which is a key transcription factor and plays a pivotal role in the homeostasis and the regulation of inflammatory signaling pathways in the liver. (2) Methods: Our study population consisted of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver. We evaluated the differential protein expression of NF-κB, ERβ (Estrogen Receptor β), NFATc1 (Nuclear factor of activated T-cells) and PGC1a (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) by immunohistochemistry. (3) Results: We found that NF-κB is the key biomarker in a complicated intra- and intertissue co-expression network that interconnects metabolic and immune signaling pathways. We also demonstrated its role in lipid metabolism and possibly in the development of skeletal muscle insulin resistance and nonalcoholic steatohepatitis (NASH). (4) Conclusions: Our findings suggest that NF-κB may be the critical link between immune and metabolic pathways and could represent a future preventive and therapeutic target against obesity-induced metabolic diseases. We hope that our study will contribute to the better understanding of the complex intertissue connections that are disrupted in obesity and its associated comorbidities.

Ticagrelor increases adenosine plasma levels and coronary blood flow in response to intravenous adenosine administration. It has been suggested that ticagrelor may influence endothelial function in patients with CAD. We aimed to assess the offset of ticagrelor’s effect on endothelial function.