Biomarkers In Atrial Fibrillation Research Articles

Left Atrial Volume as a Biomarker of Atrial Fibrillation at Routine Chest CT: Deep Learning Approach.

To test the performance of a deep learning (DL) model in predicting atrial fibrillation (AF) at routine nongated chest CT. A retrospective derivation cohort (mean age, 64 years; 51% female) consisting of 500 consecutive patients who underwent routine chest CT served as the training set for a DL model that was used to measure left atrial volume. The model was then used to measure atrial size for a separate 500-patient validation cohort (mean age, 61 years; 46% female), in which the AF status was determined by performing a chart review. The performance of automated atrial size as a predictor of AF was evaluated by using a receiver operating characteristic analysis. There was good agreement between manual and model-generated segmentation maps by all measures of overlap and surface distance (mean Dice = 0.87, intersection over union = 0.77, Hausdorff distance = 4.36 mm, average symmetric surface distance = 0.96 mm), and agreement was slightly but significantly greater than that between human observers (mean Dice = 0.85 [automated] vs 0.84 [manual]; P = .004). Atrial volume was a good predictor of AF in the validation cohort (area under the receiver operating characteristic curve = 0.768) and was an independent predictor of AF, with an age-adjusted relative risk of 2.9. Left atrial volume is an independent predictor of the AF status as measured at routine nongated chest CT. Deep learning is a suitable tool for automated measurement.© RSNA, 2019See also the commentary by de Roos and Tao in this issue.

Does an imbalance in circulating vascular endothelial growth factors (VEGFs) cause atrial fibrillation in patients with valvular heart disease?

The pathogenesis of atrial fibrillation (AF) remains unclear. Vascular endothelial growth factors (VEGFs) can stimulate fibrosis within the atrium and ventricle. We hypothesized that there is a relationship between the serum VEGFs/soluble vascular endothelial growth factor receptor (sVEGFRs) levels and AF in patients with valvular heart disease (VHD). This provides a new paradigm for studying AF. The plasma levels of VEGF-A, VEGF-C, sVEGFR-1 and sVEGFR-2 were detected by enzyme-linked immunosorbent assay (ELISA). A total of 100 people, consisting of AF patients (long-standing, persistent AF; n=49), sinus rhythm (SR) patients (n=31) and healthy controls (n=20), were included in this study. The plasma levels of VEGF-A were significantly higher in AF patients compared to healthy control (P<0.05). The plasma levels of sVEGFR-1 were significantly higher in AF compared to SR (P<0.05). The plasma levels of sVEGFR-2 were significantly lower in AF patients compared to SR patients and healthy controls (both P<0.05). There was a significant and negative correlation between AF and the sVEGFR-2 levels in the groups (r=-0.432, P=0.000). An imbalance in VEGFs and sVEGFRs may contribute to AF by breaking the balance of angiogenesis and lymphangiogenesis. Additionally, sVEGFR-2 may be an important biomarker of AF.

MicroRNA expression signatures of atrial fibrillation: The critical systematic review and bioinformatics analysis.

Association between microRNA (miRNA) expression signatures and atrial fibrillation has been evaluated with inconsistent findings in different studies. This study aims to identify miRNAs that actually play vital role in pathophysiological process of atrial fibrillation and explore miRNA-targeted genes and the involved pathways. Relevant studies were retrieved from the electronic databases of Embase, Medline, and Cochrane Library to determine the miRNA expression profiles between atrial fibrillation subjects and non-atrial fibrillation controls. Robustness of results was assessed using sensitivity analysis. Subgroup analyses were performed based on species, miRNA detection method, sample source, and ethnicity. Quality assessment of studies was independently conducted according to QUADAS-2. Bioinformatics analysis was applied to explore the potential genes and pathways associated with atrial fibrillation, which were targeted by differentially expressed miRNAs. Form of pooled results was shown as log10 odds ratios (logORs) with 95% confidence intervals (CI), and random-effects model was used. In total, 40 articles involving 283 differentially expressed miRNAs were reported. And 51 significantly dysregulated miRNAs were identified in consistent direction, with 22 upregulated and 29 downregulated. Among above-mentioned miRNAs, miR-223-3p (logOR 6.473; P &lt; 0.001) was the most upregulated, while miR-1-5p (logOR 7.290; P &lt; 0.001) was the most downregulated. Subgroup analysis confirmed 53 significantly dysregulated miRNAs (21 upregulated and 32 downregulated) in cardiac tissue, with miRNA-1-5p and miRNA-223-3p being the most upregulated and downregulated miRNAs, respectively. Additionally, miR-328 and miR-1-5p were highly blood-specific, and miR-133 was animal-specific. In the detection method sub-groups, miRNA-29b and miRNA-223-3p were differentially expressed consistently. Four miRNAs, including miRNA-223-3p, miRNA-21, miRNA-328, and miRNA-1-5p, were consistently dysregulated in both Asian and non-Asian. Results of sensitivity analysis showed that 47 out of 51 (92.16%) miRNAs were dysregulated consistently. Totally, 51 consistently dysregulated miRNAs associated with atrial fibrillation were confirmed in this study. Five important miRNAs, including miR-29b, miR-328, miR-1-5p, miR-21, and miR-223-3p may act as potential biomarkers for atrial fibrillation. Impact statement Atrial fibrillation (AF) is considered as the most common arrhythmia, and it subsequently causes serious complications including thrombosis and heart failure that increase the social burden. The definite mechanisms underlying AF pathogenesis remain complicated and unclear. Many studies attempted to discover the transcriptomic changes using microarray technologies, and the present studies for this hot topic have assessed individual miRNAs profiles for AF. However, results of different articles are controversial and not each reported miRNA is actually associated with the pathogenesis of AF. The present systematic review and meta-analysis identified that 51 consistently dysregulated miRNAs were associated with AF. Of these miRNAs, five miRNAs (miRNA-1-5p, miRNA-328, miRNA-29b, miRNA-21, and miRNA-223-3p) may act as novel biomarkers for AF. The findings could offer a better description of the biological characteristics of miRNAs, meanwhile might serve as new target for the intervention and monitoring AF in future studies.

P4415Long obstructive sleep apneas as a biomarker of atrial fibrillation

Abstract Background Even though obstructive sleep apnea (OSA) is strongly associated with atrial fibrillation (AF), the use of traditional OSA scoring by apnea hypopnea index (AHI) did not result in improved arrhythmia outcomes in recent randomized trials. Longer OSA episodes lead to stronger pro-arrhythmic changes, and whether very long OSA episodes are more prevalent in AF patients remains unknown. Purpose We hypothesized that AF patients with mild-moderate OSA manifest greater percentage of long (&gt;20s), very long (&gt;30s), and extremely long (&gt;40s) OSA episodes, compared to control OSA patients matched to AHI, age and sex. Methods From patients studied with diagnostic polysomnography in our laboratory between 2016 and 2018, we selected 22 patients with mild-moderate untreated OSA of which 11 patients had history of paroxysmal AF and 11 patients did not have any cardiac history. The length, oxygen desaturation, and relationship to neighboring events was manually re-measured in all recorded apnea and hypopnea events. Results In the 22 included patients (age 62.5±9.1 years, AHI 12.8±6.1, 40% female) we recorded 1021 apneas: 508 in the AF group and 513 in the control group. AF patients had longer apneas compared to the patients without AF history (mean length 28.7±11.7s vs. 23.3±9.9s; p&lt;0.0001). The proportion of apneas that were long (&gt;20s), very long (&gt;30s), and extremely long (&gt;40s) was greater in the AF group as compared to the control (p=0.0039, p=0.0215, p=0.0104, respectively; see figure). The acute oxygen saturation drops (&gt;2%) during apneas were comparable between the AF group and control groups (p=0.13), but the long (&gt;20s) apneas were prone to greater oxygen desaturations. Length of Apneas Conclusions While traditional scoring of OSA focuses on episodes lasting &gt;10s, our data newly show that longer durations of OSA events are particularly prevalent in AF patients. These results, combined with recent mechanistic studies showing that longer apneas exert greater pro-arrhythmic effect on atrial conduction, suggest that novel scoring of OSA placing more weight on longer apneas should be explored, especially when screening and titrating OSA therapy in patients at risk of AF.

Differentially expressed miRNAs in circulating exosomes between atrial fibrillation and sinus rhythm.

Exosomes are small (30-150 nm) membrane vesicles released by cells that transmit intercellular information. As one of the contents of exosomes, microRNAs (miRNAs) may play an important role in the pathogenesis of atrial fibrillation (AF). Exosomal miRNAs potentially function as biomarkers in AF, as shown in many other diseases. To identify the different expression level of plasma exosomal miRNAs between persistent AF and sinus rhythm (SR) patients, we performed high-throughput sequencing of small RNAs in the exosomes of AF (n=4) and SR (n=4) patients. Target genes of the DE miRNAs were predicted and put into gene ontology analysis and pathway analysis. In the validation phase, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) of 6 of the DE miRNAs in AF (n=40) and SR (n=20) patients. Univariate and multivariate logistic analysis were used to analyze risk factors of AF. With high-throughput sequencing, we revealed 39 differentially expressed (DE) miRNAs in circulating exosomes. We validated 4 of the DE plasma exosomal miRNAs (miR-483-5p, miR-142-5p, miR-223-3p, miR-223-5p) using qRT-PCR. Univariate logistic analysis shows miR-483-5p, miR-142-5p, miR-223-3p are related with AF, while multivariate logistic analysis suggests miR-483-5p is independently in correlation with AF. This discovery opens up a new perspective in the complicated mechanism underlying AF and the DE plasma exosomal miRNAs exert enormous potential of acting as biomarkers in assessing severity or prognostic of AF and help selecting therapeutic strategy.

P4421Increased circulating levels of VCAM-1 correlate with left atrial remodeling in highly trained athletes

Abstract Introduction Reports have shown increased risk of atrial fibrillation (AF) in athletes. Vascular cell adhesion molecule-1 (VCAM1) is associated with new onset AF in general population. VCAM1 and its relation with left atrial (LA) remodeling have not been investigated in athletes. Purpose To study VCAM1 and LA remodeling in marathon runners. Methods Study of 36 male marathon runners in the training period previous to race (42 km) and 18 sedentary controls with no risk factors. Athletes were divided in two groups according to highest training intensity reached (group 1, &gt;100 km/week; group 2, 50–100 km/week). Previous to race in all subjects, VCAM1 serum levels were measured by ELISA and an echocardiogram was performed. In athletes, VCAM1 was measured immediately post-race. Wilcoxon and Spearman were used. Results See table. Group 1 showed a significant increment in VCAM1 post-race (651±350 to 905±373 ng/mL; p=0.002) as compared to group 2 with no increment (533±133 to 651±138 ng/mL; p=0.117). In athletes, a moderate correlation between LA volume and VCAM1 was found (rho: 0.483; p=0.007). Baseline characteristics Group 1 (n=18) Group 2 (n=18) Controls (n=18) p value Age (years) 37±6 38±5 36±4 0.373 Heart rate (bpm) 53±8 57±7 69±6 * 0.001 Body surface area (m2) 1.8±0.1 1.8±0.1 1.9±0.1 0.075 LV diastolic diameter (mm) 49±5 48±5 46±4 0.404 LV systolic diameter (mm) 29±5 30±5 30±4 0.879 Septal wall (mm) 9.1±1.2† 8.2±1.1 8.1±0.8 0.005 Posterior wall (mm) 9.3±2.1† 8.5±1.2 7.6±0.8 0.001 Ejection fraction (%) 55±3 55±6 57±4 0.110 LV mass index (g/m2) 106±27† 78±18 58±11 0.001 LA volume (mL/m2) 42±8† 30±11 25±9 0.001 E wave (cm/sec) 78±13 84±12 77±15 0.217 A wave (cm/sec) 50±12 53±10 48±16 0.438 DT (msec) 233±65 229±65 221±66 0.184 VCAM1 (ng/mL) 651±350† 533±133 440±98 0.022 Mean ± SD. *p&lt;0.05 vs group 1 and 2 post Kruskall-Wallis; †p&lt;0.05 vs other groups post Kruskall-Wallis. LV, left ventricle; LA, left atrium; DT, deceleration time. Conclusions Most trained athletes had increased levels of VCAM1 as compared to controls and less trained athletes. They also showed an increment post-effort. VCAM1 is related to LA remodeling in athletes. VCAM1 could be a potential biomarker of AF in athletes which should be confirmed. Acknowledgement/Funding FONDECYT 1170963 (LG); FONDAP 15130011 (LG,SL)

Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis.

An accurate etiological classification is key to optimize secondary prevention after ischemic stroke, but the cause remains undetermined in one third of patients. Several studies pointed out the usefulness of circulating gene expression markers to discriminate cardioembolic (CE) strokes, mainly due to atrial fibrillation (AF), while only exploring them in small cohorts. A systematic review of studies analyzing high-throughput gene expression in blood samples to discriminate CE strokes was performed. Significantly dysregulated genes were considered as candidates, and a selection of them was validated by RT-qPCR in 100 patients with defined CE or atherothrombotic (LAA) stroke etiology. Longitudinal performance was evaluated in 12 patients at three time points. Their usefulness as biomarkers for AF was tested in 120 cryptogenic strokes and 100 individuals at high-risk for stroke. Three published studies plus three unpublished datasets were considered for candidate selection. Sixty-seven genes were found dysregulated in CE strokes. CREM, PELI1, and ZAK were verified to be up-regulated in CE vs LAA (p = 0.010, p = 0.003, p < 0.001, respectively), without changes in their expression within the first 24h after stroke onset. The combined up-regulation of these three biomarkers increased the probability of suffering from CE stroke by 23-fold. In cryptogenic strokes with subsequent AF detection, PELI1 and CREM showed overexpression (p = 0.017, p = 0.059, respectively), whereas in high-risk asymptomatic populations, all three genes showed potential to detect AF (p = 0.007, p = 0.007, p = 0.015). The proved discriminatory capacity of these gene expression markers to detect cardioembolism even in cryptogenic strokes and asymptomatic high-risk populations might bring up their use as biomarkers.

Epigenetic implication in atrial fibrillation: a potential biomarker?

Atrial fibrillation (AF) remains the center of attention in cardiology and vascular medicine, besides coronary artery disease (CAD) and heart failure (HF). Not only how to manage the disease, but how to prevent it also attract the interest of the researcher. A biomarker is still a hot topic in AF. Although the current recommendation did not place biomarkers in a central role, the search for perfect biomarkers for AF is still ongoing. The epigenetic mechanism seems to have a pivotal role in explaining the gap in AF mechanism understanding. How previous cardiac condition, behavioral factor, and environmental factor interact with each other and result in the genesis of AF can be explained by an epigenetic mechanism. Epigenetic process altered the gene expression and, in the future, will result in the development of the disease. Three epigenetic mechanisms that had been identified are DNA methylation, histone modification, and microRNA (miRNA). Identification of these early changes is the subject of epigenetic biomarkers. This review will discuss the basic understanding of the epigenetic mechanism in AF and its potential role to be the new biomarkers.

Identification of microRNA biomarkers in atrial fibrillation: A protocol for systematic review and bioinformatics analysis.

Background:Atrial fibrillation (AF) is recognized as the most prevalent arrhythmia, and its subsequently serious complications of heart failure and thromboembolism always raise the social attention. To date, the molecular pathogenesis of AF has largely remained unclear. Publications of contemporary studies have evaluated individual miRNAs expression signatures for AF, and findings of different studies are inconsistent and not all miRNAs reported are actually important in the pathogenesis of AF.Methods:Medline, Embase, and Cochrane Library databases will be comprehensively searched (up to April 30, 2019) for studies identifying miRNA expression profiling in subjects with and without AF. Log10 odds ratios (logORs) and associated 95% confidence interval (95%CI) will be calculated using random-effects models. Subgroup analysis will be performed according to miRNA detecting methods, species, sample types, and ethnicities. Sensitivity analysis will be conducted to detect the robustness of the findings. The methodological quality of studies will be independently assessed using criteria adopted from the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Furthermore, bioinformatics analysis will be performed to identify the potential target genes in AF and the corresponding pathways of dysregulated miRNAs. Two reviewers will independently screen potential studies and extract data in a structured eligibility items, with any disagreements being resolved by consensus.Results:The present systematic review will identify potential biomarkers by pooling all differentially expressed miRNAs in AF studies, as well as to predict miRNA-target interactions and to identify the potential biometric functions using bioinformatics analysis.Conclusions:This systematic review and bioinformatics analysis will identify several miRNAs as potential biomarkers for AF, and explore the biological pathways regulated by the eligible miRNAs.PROSPERO registration number:CRD42019127594

Identification of microRNAs and genes as biomarkers of atrial fibrillation using a bioinformatics approach

ObjectiveWe aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF).MethodsData for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed.ResultsTen differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3.ConclusionThe identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.

Serum fatty acid binding proteins as a potential biomarker in atrial fibrillation.

Atrial fibrillation (AF) is a commonly occurring arrhythmia which significantly reduces patients' quality of life and substantially shortens life expectancy. Although long chain fatty acids (LCFAs) are the basic energy substrates for myocardial metabolism, their excess can result in lipotoxicity, which increases the risk of arrhythmia. Intracellularly, LCFAs are bound by fatty acid biding proteins (FABPs) and this results in low level of free LCFAs in the cytoplasm. Based on this principle, FABPs are considered "safeguards" against overwhelming accumulation of esterified into different bioactive lipid fractions (e.g. ceramide, diacylglycerols) LCFAs. So far, several FABPs have been discovered in humans. Currently, in relation to cardiovascular diseases heart-type fatty acid binding protein (H-FABP) and adipocyte fatty acid binding protein (A-FABP) play significant roles. Nowadays, A-FABP is of great interest for research related with obesity, diabetes and coexisting disorders including cardiovascular diseases. Concomitantly, H-FABP is already well-established marker in the early diagnosis of myocardial infarction. Moreover, FABPs were assigned as a potential biomarker of AF in patients with de novo diagnosed arrhythmia, chronic heart failure (CHF), and in patients undergoing cardiac surgery. Another group of studies where the concentrations of plasma FABPs were analyzed are patients subjected to electrical cardioversion (ECV) and radio-catheter ablation therapy (RFA). It is worth mentioning that, in addition to traditional anti-arrhythmic drugs (AADs) or ECV, ablation techniques are used with good effects. Even though the treatment of arrhythmias is constantly developing, the maintenance of the sinus rhythm (SR) is still a serious problem. Therefore, it is worth looking for a biomarker which is suitable for the patient's treatment qualifications as well as assessing its effectiveness. Thus, the aim of this work is to present current data on the clinical significance of FABPs in terms of the development and treatment of AF.

Inflammatory Biomarkers in Atrial Fibrillation.

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

Biomarkers of Atrial Fibrillation in Metabolic Syndrome.

Whether the increased atrial fibrillation (AF) risk in metabolic syndrome (MetS) patients is due to the syndrome as a whole or simply the sum of the risks of its individual component parts is still obscure. These two clinical entities share many pathophysiological links and thus distinction between a casual observation and a significant association is difficult. Biomarkers associated with pathogenesis of AF in the context of MetS have the ability to refine future risk prediction. In the present review we identify circulating substances that could be regarded as potential biomarkers for prediction of incident AF, or of cardiovascular events in the setting of AF in patients with MetS. Cardiac myocyte injury and stress markers (troponin and natriuretic peptides), markers of renal function (glomeral filtration rate, cystatin-C), and inflammation markers/mediators (interleukin- 6, CRP) are promising biomarkers of patients with AF and MetS.

Biomarkers in Atrial Fibrillation and Heart Failure.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice and an important contributor to cardiovascular morbidity and mortality. Although the exact mechanisms behind AF are not completely elucidated, the underlying pathophysiological changes have been well described. Predisposal factors for AF include the older age, the increased left atrial size, the decreased left atrial function, the presence of heart failure and left ventricular systolic dysfunction and the presence of coronary heart disease or pulmonary or mitral valve disease. In addition to these factors, emerging evidence demonstrate that myocardial strain, fibrosis and inflammation, are associated with AF as well as the pathogenesis of the arrhythmia. The natruretic peptide system including Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP) and C-type Natriuretic Peptide (CNP) is indicative of the level of myocardial strain which may predispose to AF. As a result, the aforementioned peptides are increased in AF patients. The levels of myocardial fibrosis biomarkers, such as ST2 and Galectin-3, are elevated suggesting atrial structural abnormalities, while the increased levels of CRP and Interleukin-6 supplement the inflammatory profile of AF patients. Emerging data for the aforementioned biomarkers are discussed in the present review.

Biomarkers of Atrial Fibrillation in Hypertension.

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia globally and substantially increases the risk for thromboembolic disease. Albeit, 20% of all cases of AF remain undiagnosed. On the other hand, hypertension amplifies the risk for both AF occurrences through hemodynamic and non-hemodynamic mechanisms and cerebrovascular ischemia. Under this prism, prompt diagnosis of undetected AF in hypertensive patients is of pivotal importance. We conducted a review of the literature for studies with biomarkers that could be used in AF diagnosis as well as in predicting the transition of paroxysmal AF to sustained AF, especially in hypertensive patients. Potential biomarkers for AF can be broadly categorized into electrophysiological, morphological and molecular markers that reflect the underlying mechanisms of adverse atrial remodeling. We focused on P-wave duration and dispersion as electrophysiological markers, and left atrial (LA) and LA appendage size, atrial fibrosis, left ventricular hypertrophy and aortic stiffness as structural biomarkers, respectively. The heterogeneous group of molecular biomarkers of AF encompasses products of the neurohormonal cascade, including NT-pro BNP, BNP, MR-pro ANP, polymorphisms of the ACE and convertases such as corin and furin. In addition, soluble biomarkers of inflammation (i.e. CRP, IL-6) and fibrosis (i.e. TGF-1 and matrix metalloproteinases) were assessed for predicting AF. The reviewed individual biomarkers might be a valuable addition to current diagnostic tools but the ideal candidate is expected to combine multiple indices of atrial remodeling in order to effectively detect both AF and adverse characteristics of high risk patients with hypertension.

Biomarkers in Atrial Fibrillation; From Pathophysiology to Diagnosis and Treatment

Biomarkers in Atrial Fibrillation; From Pathophysiology to Diagnosis and Treatment

Biomarkers of Atrial Fibrillation: Which One Is a True Marker?

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmias and associated with the risk of stroke and death. Continuous development of the diagnostic tool and prognostic stratification may lead to optimal management of AF. The use of biomarkers in the management of AF has been grown as an interesting topic. However, the AF biomarkers are not yet well established in the major guidelines. Among these biomarkers, a lot of data show troponin and brain natriuretic peptides are promising for the prediction of future events. The troponin elevation in AF patients may not necessarily be diagnosed as myocardial infarction or significant coronary artery stenosis, and brain natriuretic peptide elevation may not necessarily confirm heart failure. Troponin T and troponin I may predict postoperative AF. Furthermore, troponin and brain natriuretic peptide gave better prognostic performance when compared with the risk score available today.

Physical Activity, Quality of Life, and Biomarkers in Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction (from the NEAT-HFpEF Trial)

Although atrial fibrillation/atrial flutter (AF/AFL) and heart failure with preserved ejection fraction (HFpEF) frequently coexist, the influence of AF/AFL on physical activity, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life in HFpEF is unclear and could have relevance to HFpEF trial design. We evaluated the association between AF/AFL and volitional physical activity, functional performance, NT-proBNP, and quality of life in patients with HFpEF in the Nitrate's Effect on Activity Tolerance (NEAT)-HFpEF trial. Of 99 patients with accelerometer data, 35 (35%) had AF/AFL. There were no differences between AF/AFL versus no AF/AFL in baseline average daily accelerometer units (ADAUs; 9.06 ± 0.54 vs 9.06 ± 0.48, p = 0.75), hours active per day (9.7 ± 2.3 vs 9.2 ± 2.2, p = 0.86), or 6-minute walk distance (6MWD; 307 ± 136m vs 321 ± 110m, p = 0.85). AF/AFL status was associated with higher baseline NT-proBNP (586 [25th to 75th percentile: 291 to 1254] pg/ml vs 154 [25th to 75th percentile: 92 to 288] pg/ml, p <0.001) and Kansas City Cardiomyopathy Questionnaire scores (69 [25th to 75th percentile: 46 to 88] vs 48 [25th to 75th percentile: 37 to 70], p = 0.01). Although treatment responses to isosorbide mononitrate measured by change in ADAUs, hours active per day, or 6MWD did not vary by AF/AFL status (interaction p >0.05 for all), AF/AFL patients had greater reductions in NT-proBNP after isosorbide mononitrate than patients without AF/AFL (interaction p <0.001), possibly due to regression to the mean. In conclusion, baseline measures and treatment-related changes in volitional physical activity (ADAUs) and functional performance (6MWD) did not differ by AF/AFL in NEAT-HFpEF, whereas NT-proBNP did. In HFpEF-where AF/AFL prevalence is high-functional measures may be superior to natriuretic peptides as trial endpoints.

YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis

Recent years, the role of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF) has been gradually elucidated. In the current study, we measured the expression of ten AF-related lncRNAs to do qRT-PCR analysis. LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was found to be significantly upregulated in AF model and Ang-II-induced mice heart. CACNA1C has been reported as a biomarker in atrial fibrillation. Here, we found that the expression pattern of CACNA1C was consistent with that of KCNQ1OT1. Electrophysiological study was conducted to demonstrate the effect of KCNQ1OT1 and CACNA1C on the Effective refractory period (ERP), interatrial conduction time (IACT), incidence of AF and AF duration of Ang-II-induced mice heart. Mechanically, KCNQ1OT1 contributed to the upregulation of CACNA1C by binding with miR-384. Furthermore, YY1 could activate the transcription of KCNQ1OT1 and CACNA1C. In conclusion, the present study revealed that YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by regulating miR-384/CACNA1C axis.

Proteomic profile of patients with atrial fibrillation undergoing cardiac surgery.

Proteomic analysis of patients with advanced cardiovascular disease was conducted to identify possible biomarkers for atrial fibrillation (AF). A total of 123 patients undergoing cardiac surgery (22 with AF and 101 without AF) and 20 healthy subjects were recruited. Demographic data, patient history and blood samples were collected. Growth/differentiation factor 15, resistin, intracellular adhesion molecule-1, galectin-3, trefoil factor 3, tissue inhibitor of metalloproteinases 1, matrix metallopeptidase 9, high-sensitive troponin T, interleukins 6, 1α, 3, 4, 8, 20 and 22, tumour necrosis factor alpha, C-X-C motif chemokines 10 and 11, S100A6 and Type III procollagen were measured in blood serum. Differential expression between any 2 groups for any of the measured proteins was identified by fitting linear models, whereas Matthews Correlation Coefficient was used to evaluate their predictive capacity. Combined markers using more than 1 protein were attained via weighted Support Vector Machines. Although serum levels of the markers were higher in patients with cardiovascular disease than in healthy subjects, only growth/differentiation factor 15 and resistin were significantly higher in patients with AF among the subpopulation who underwent heart surgery (P = 0.029 and P = 0.007, respectively). Specific pairs of several biomarkers had mediocre predictive capacity for AF. Growth/differentiation factor 15 and resistin are 2 markers that could be helpful in stratifying risk for AF in patients with cardiovascular disease. Yet, more research in terms of proteomics and investigation of possible molecular pathways implicated is required.