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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. [ABSTRACT FROM AUTHOR]

Aims The heart is constantly challenged with acute bouts of stretching or overload. Systolic adaptations to these challenges are known but adaptations in diastolic stiffness remain unknown. We evaluated adaptations in myocardial stiffness due to acute stretching and characterized the underlying mechanisms. Methods and results Left ventricles (LVs) of intact rat hearts, rabbit papillary muscles and myocardial strips from cardiac surgery patients were stretched. After stretching, there was a sustained >40% decrease in end-diastolic pressure (EDP) or passive tension (PT) for 15 min in all species and experimental preparations. Stretching by volume loading in volunteers and cardiac surgery patients resulted in E/E' and EDP decreases, respectively, after sustained stretching. Stretched samples had increased myocardial cGMP levels, increased phosphorylated vasodilator-stimulated phosphoprotein phosphorylation, as well as, increased titin phosphorylation, which was reduced by prior protein kinase G (PKG) inhibition (PKGi). Skinned cardiomyocytes from stretched and non-stretched myocardia were studied. Skinned cardiomyocytes from stretched hearts showed decreased PT, which was abrogated by protein phosphatase incubation; whereas those from non-stretched hearts decreased PT after PKG incubation. Pharmacological studies assessed the role of nitric oxide (NO) and natriuretic peptides (NPs). PT decay after stretching was significantly reduced by combined NP antagonism, NO synthase inhibition and NO scavenging, or by PKGi. Response to stretching was remarkably reduced in a rat model of LV hypertrophy, which also failed to increase titin phosphorylation. Conclusions We describe and translate to human physiology a novel adaptive mechanism, partly mediated by titin phosphorylation through cGMP-PKG signalling, whereby myocardial compliance increases in response to acute stretching. This mechanism may not function in the hypertrophic heart. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Pericardial fluid (PF) mirrors the heart's pathophysiological status due to its proximity. This study aimed to characterise the PF proteome to identify new biomarkers of disease. Eighty-three patients submitted to aortic valve replacement surgery with severe aortic stenosis were selected, and their baseline echocardiographic and clinical variables were documented. Thirteen samples were selected blindly for proteome characterisation following a shotgun (GeLC–MS/MS) and a label-free quantification approach (LFQ). According to previous AF history, a partial least squares discriminant analysis (PLS-DA) was conducted, and the top 15 variables important in projection were identified. To inquire potential biomarkers, ROC curves were designed using LFQ data. Target proteins were further validated by ELISA, in both pericardial fluid and serum. Proteome analysis uncovered nine proteins up- and downregulated ≥2-fold. Annexin A1, annexin A2, and vimentin were among the top 15 most important variables for group discrimination in PLS-DA. Protein—protein interaction and gene ontology enrichment analysis presented functional interaction among identified proteins, which were all part of focal adhesion sites. Annexin A1 was increased in the pericardial fluid of AF patients but not in serum when quantified by ELISA. Annexin A1 is a novel pericardial fluid biomarker of AF in patients with severe aortic stenosis. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to evaluate the association of GDF-15 and NT-pro-BNP in two different biological matrices with AF in severe aortic stenosis patients undergoing aortic valve replacement surgery (AVR), its association with atrial matrix remodeling, as well as with 30-day postoperative outcomes. Main Methods: One hundred and twenty-six patients between 2009 and 2019 with severe aortic stenosis undergoing AVR surgery in a tertiary hospital were assessed. Key Findings: pericardial fluid GDF-15 and pericardial fluid and serum NT-pro-BNP were increased in AF patients with aortic stenosis. COL1A1 and COL3A1 gene expression increased when pericardial fluid NT-pro-BNP values were higher. TIMP4 was positively correlated with pericardial fluid GDF-15. Significance: GDF-15 and NT-pro-BNP in the pericardial fluid are biomarkers of atrial fibrillation in aortic stenosis and correlate with atrial matrix remodeling. AKI is predicted by both serum and pericardial fluid GDF-15. [ABSTRACT FROM AUTHOR]

The remote but heart-encircling location of pericardial fluid confers this biofluid unique properties. Once past the limitation of the invasive collection, for instance, on occasion of heart surgery or pericardiocentesis, the scrutiny of pericardial fluid content can be of great interest in cardiovascular research. This liquid concentrates many heart-derived factors, thus enclosing several surrogate markers for the diagnosis or prognosis of a large spectrum of diseases either pericardial (e.g. malignant or tuberculous pericarditis) or non-pericardial/heart diseases (e.g. coronary artery disease or valvular heart diseases). Herein, for the first time, the molecular knowledge of pericardial fluid is reviewed, through an in-depth literature search and mining, and then translated into a network map of the diseases influencing pericardial fluid composition. The suitability of pericardial fluid for biomarker research could be demonstrated by evident molecular profiles between different conditions as well as by stronger correlations to cardiac structural and functional parameters, fainter or lacking in plasma/serum. Also highlighted here are the results of mechanistic research conducted with pericardial fluid in several hot topics of research, such as chronotropy, inotropy, coronary perfusion and cardiac electrophysiology. Moreover, the progress in intrapericardial therapeutics, motivated by pericardial fluid's low clearance rates, higher efficiency and lesser risk of systemic effects over conventional delivery methods, is surveyed and discussed. [ABSTRACT FROM AUTHOR]