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A novel biomarker for prediction of atrial fibrillation susceptibility in patients with celiac disease.

ABSTRACT: Celiac disease (CD), a serious autoimmune disorder that occurs in people who are genetically predisposed, is induced by dietary gluten intake and affects primarily the small intestine. Many studies have identified an increased risk of cardiovascular problems in patients with CD. Moreover, these patients are susceptible to certain liver diseases, as well as fibrosis.The aim of this study was to assess the presence of fibrosis using the De Ritis ratio, determining its effect on the electromechanical features of the left atrium and its susceptibility to atrial fibrillation (AF) in patients with CD.A total of 97 patients diagnosed with CD by antibody test and biopsy were included in this prospective study. Two groups were created from these patients, a fibrosis-prone (FP) group and a non-fibrosis-prone (NFP) group, according to the cut-off value, as defined in previously published reports, for the AST/ALT ratio. Electrocardiographic and echocardiographic examinations were performed as part of the study.There were no differences in the baseline characteristics and conventional echocardiographic parameters of the defined groups. However, the patients in the FP group, as compared to those in the NFP group, had significantly increased PWD (56.68±6.48 ms vs. 37.49±6.22 ms, P<0.001). Additionally, significantly higher interatrial (60.50±13.05 ms vs. 29.40±11.55 ms, P<0.001), intra-left atrial (44.18±14.12 ms vs. 21.02±11.99 ms, P<0.001), and intra-right atrial (15.61±8.91 ms vs. 8.38±4.50 ms, P<0.001) EMD was found among the patients in the FP group compared to that of the NFP group.It is believed that the susceptibility to AF cited in previous studies may be related to fibrosis. Our study is the first to examine the possible effects of fibrosis on AF susceptibility in patients with CD, whereby we propose a new biomarker for prediction of AF susceptibility of these patients.

SUBMITTER: Kucukseymen S

PROVIDER: S-EPMC5760044 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A novel biomarker for prediction of atrial fibrillation susceptibility in patients with celiac disease.

Kucukseymen Selcuk S Cekin Ayhan Hilmi AH Bayar Nermin N Arslan Sakir S Uygur Kucukseymen Elif E Mercan Tanju T Ozdemir Semir S

PloS one 20180109 1

<h4>Background</h4>Celiac disease (CD), a serious autoimmune disorder that occurs in people who are genetically predisposed, is induced by dietary gluten intake and affects primarily the small intestine. Many studies have identified an increased risk of cardiovascular problems in patients with CD. Moreover, these patients are susceptible to certain liver diseases, as well as fibrosis.<h4>Objective</h4>The aim of this study was to assess the presence of fibrosis using the De Ritis ratio, determin ...[more]

PMID: 29315324

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Project description:BACKGROUND:Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF. METHODS:Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation. RESULTS:Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13). CONCLUSIONS:Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Project description:Sepsis is defined by life-threatening organ dysfunction during infection and is the leading cause of death in hospitals. During sepsis, there is a high risk that new onset of atrial fibrillation (AF) can occur, which is associated with significant morbidity and mortality. Consequently, early prediction of AF during sepsis would allow testing of interventions in the intensive care unit (ICU) to prevent AF and its severe complications. In this paper, we present a novel automated AF prediction algorithm for critically ill sepsis patients using electrocardiogram (ECG) signals. From the heart rate signal collected from 5-min ECG, feature extraction is performed using the traditional time, frequency, and nonlinear domain methods. Moreover, variable frequency complex demodulation and tunable Q-factor wavelet-transform-based time-frequency methods are applied to extract novel features from the heart rate signal. Using a selected feature subset, several machine learning classifiers, including support vector machine (SVM) and random forest (RF), were trained using only the 2001 Computers in Cardiology data set. For testing the proposed method, 50 critically ill ICU subjects from the Medical Information Mart for Intensive Care (MIMIC) III database were used in this study. Using distinct and independent testing data from MIMIC III, the SVM achieved 80% sensitivity, 100% specificity, 90% accuracy, 100% positive predictive value, and 83.33% negative predictive value for predicting AF immediately prior to the onset of AF, while the RF achieved 88% AF prediction accuracy. When we analyzed how much in advance we can predict AF events in critically ill sepsis patients, the algorithm achieved 80% accuracy for predicting AF events 10 min early. Our algorithm outperformed a state-of-the-art method for predicting AF in ICU patients, further demonstrating the efficacy of our proposed method. The annotations of patients' AF transition information will be made publicly available for other investigators. Our algorithm to predict AF onset is applicable for any ECG modality including patch electrodes and wearables, including Holter, loop recorder, and implantable devices.

Project description:Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02358-y.

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A novel biomarker for prediction of atrial fibrillation susceptibility in patients with celiac disease.

Publications

A novel biomarker for prediction of atrial fibrillation susceptibility in patients with celiac disease.

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