Sex-related differences of fatty acid-binding protein 4 and leptin levels in atrial fibrillation

Aims: Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Our aim was to study the sex differences in adipokines levels according to AF burden. Methods and results: Two independent cohorts of patients were studied: (i) consecutive patients with AF undergoing catheter ablation (n = 217) and (ii) a control group (n = 105). (i) Adipokines, oxidative stress, indirect autonomic markers, and leucocytes mRNA levels were analysed; (ii) correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients; and (iii) logistic regression and random forest model were used to determine predictors of AF recurrence after ablation. Our results showed that: (i) fatty acid-binding protein 4 (FABP4) and leptin levels were higher in women than in men in both cohorts (P < 0.01). In women, FABP4 levels were higher on AF cohort (20 ± 14 control, 29 ± 18 paroxysmal AF and 31 ± 17 ng/mL persistent AF; P < 0.01). In men, leptin levels were lower on AF cohort (22 ± 15 control, 13 ± 16 paroxysmal AF and 13 ± 11 ng/mL persistent AF; P < 0.01). (ii) In female with paroxysmal AF, there was a lower acetylcholinesterase and higher carbonic anhydrase levels with respect to men (P < 0.05). (iii) Adipokines have an important role on discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor of recurrence after ablation (1.067, 95% confidence interval 1-1.14; P = 0.046). Conclusion: The major finding of the present study is the sex-based differences of FABP4 and leptin levels according to AF burden. These adipokines are associated with oxidative stress, inflammatory and autonomic indirect markers, indicating that they may play a role in AF perpetuation.This study was supported by projects (PI16/01282 and PI18/01584) integrated in the Plan Estatal de I+D+I 2016–2019 and cofounded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación del Fondo Europeo de Desarrollo Regional (FEDER). J.N.L.-C. and M.R.-M. were a recipient of a Sociedade Galega de Cardioloxía (SOGACAR) research grant. D.d.G.-C. was a recipient of a Juan de la Cierva-Incorporación grant from the Ministry of Science Innovation and Universities (IJCI-2016-29393). CIBER Cardiovascular (CB16/11/00403 to V.Ll.-C. and D.d.G.-C.) is a project from Carlos III Health Institute.Peer reviewe

Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value.

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control.This work was supported by the European Union Horizon 2020 research and innovation program under Grant Agreement#965286. The study was also supported by the Ministry of Science and Innovation (MCIN) (PID2019- 109329RB-I00 and PGC2018-097019-B-I00) funded by MCIN / AEI / 10.13039/501100011033, the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3) (PT17/0019/0003- ISCIII-SGEFI / ERDF, ProteoRed), the Fundación Interhospitalaria para la Investigación Cardiovascular, the Fundación Salud 2000 and by “la Caixa” Banking Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020- 001041-S funded by MICIN/AEI/10.13039/501100011033). We also thank Asunción Conde and Sergey Mironov for their support on monitoring database quality and advice in ECG signal processing, respectively.S

Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control. Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. Here, the authors use non-invasive atrial electromechanical assessment during AF to identify early remodeling changes associated with underlying myopathy, which in the clinic decrease the probability of acute and mid-term successful rhythm control

Transcriptomic and Proteomic Analysis of the Epicardial Adipose Tissue

The study of epicardial adipose tissue (EAT) has been limited by its accessibility due to its proximity to the heart. Moreover, many common animal models do not have EAT, leaving its functional role underestimated and poorly elucidated. Recent advances in medicine and science have allowed for better studies that provide a more comprehensive understanding of its physiological role. One way to dissect its function is the study of its gene expression. In this chapter, we summarize transcriptomic and proteomic analyses which show that EAT expresses a unique set of genes setting it apart from other adipose tissues in the body. This distinctive set of genes modulates a feedback mechanism that has direct interaction with the myocardium. The EAT shares its blood supply with the coronary arteries and innervation with the cardiac muscle, provides physical protection, and regulates energetic metabolites needed by the myocardium. Transcriptomic and proteomic studies show that it is a local source of adipokines with paracrine influence on the myocardium due to the intimate microcirculation shared by both tissues. These analyses also show that it has a role in the immune and endocrine systems affecting the rest of the body. Furthermore, regulation of EAT gene expression is not monolithic and can be affected by multiple factors such as sex, age, underling disease, medication, etc. Gene expression studies can therefore provide great insight into the function of EAT and its role in health and disease