Dataset Information

Association between serum inflammatory biomarkers and atrial low voltage in patients with atrial fibrillation: A phase 1 FIB-MARK study.

ABSTRACT:

Background

The mechanisms leading to atrial fibrosis in patients with atrial fibrillation (AF), especially in relation to inflammation, remain unclear.

Methods and results

Forty biomarkers were measured in peripheral blood samples collected prior to catheter ablation, and the association with left atrial (LVZ) was evaluated in 16 consecutive patients. The median %LVZ was 17%. In Pearson's correlation analysis, interleukin(IL)-17A and interferon(IFN)-γ showed the most significant positive and negative correlations with %LVZ (R = 0.35 and 0.43, P < 0.001). Furthermore, the IL-17A/IFN-γ ratio was significantly associated with %LVZ (R = 0.65, P = 0.007), as was the macrophage inflammatory protein (MIP)-1δ/IFN-γ ratio (R = 0.73, P = 0.001). The area under the receiver operator characteristics curves of the IL-17A/IFN-γ and MIP-1δ/IFN-γ ratios for detecting severe LVZ (%LVZ ≥ 10% as a reference standard) were 0.88 and 0.90, respectively. The IL-17A/IFN-γ ratio was significantly higher in patients with severe LVZ than those without (1.41 versus 0.97, P = 0.01). Furthermore, the sensitivity, specificity, and accuracy for detecting severe LVZ were 60%, 100%, and 75.0%, respectively, at a cut-off value of 1.3.

Conclusions

Among inflammatory biomarkers, the serum IL-17A/IFN-γ ratio was associated with severe left atrial LVZ in patients with AF. However, further studies are needed to clarify the role of inflammatory biomarkers in the development and progression of atrial fibrosis in patients with AF.

SUBMITTER: Kawaji T

PROVIDER: S-EPMC8571495 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Association between serum inflammatory biomarkers and atrial low voltage in patients with atrial fibrillation: A phase 1 FIB-MARK study.

Kawaji Tetsuma T Ono Koh K Sowa Naoya N Aizawa Takanori T Hojo Shun S Yaku Hidenori H Nakatsuma Kenji K Kaneda Kazuhisa K Kato Masashi M Yokomatsu Takafumi T Shizuta Satoshi S Miki Shinji S Kimura Takeshi T

International journal of cardiology. Heart & vasculature 20211101

<h4>Background</h4>The mechanisms leading to atrial fibrosis in patients with atrial fibrillation (AF), especially in relation to inflammation, remain unclear.<h4>Methods and results</h4>Forty biomarkers were measured in peripheral blood samples collected prior to catheter ablation, and the association with left atrial (LVZ) was evaluated in 16 consecutive patients. The median %LVZ was 17%. In Pearson's correlation analysis, interleukin(IL)-17A and interferon(IFN)-γ showed the most significant p ...[more]

PMID: 34765718

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Project description:BACKGROUND AND PURPOSE:Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. METHODS:Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age- and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. RESULTS:GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. CONCLUSIONS:Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.

Project description:BackgroundLow-voltage-substrate (LVS)-guided ablation for persistent atrial fibrillation (AF) has been described either in sinus rhythm (SR) or AF. Prolonged fractionated potentials (PFPs) may represent arrhythmogenic slow conduction substrate and potentially co-localize with LVS. We assess the spatial correlation of PFP identified in AF (PFP-AF) to those mapped in SR (PFP-SR). We further report the relationship between LVS and PFPs when mapped in AF or SR.Materials and methodsThirty-eight patients with ablation naïve persistent AF underwent left atrial (LA) high-density mapping in AF and SR prior to catheter ablation. Areas presenting PFP-AF and PFP-SR were annotated during mapping on the LA geometry. Low-voltage areas (LVA) were quantified using a bipolar threshold of 0.5 mV during both AF and SR mapping. Concordance of fractionated potentials (CFP) (defined as the presence of PFPs in both rhythms within a radius of 6 mm) was quantified. Spatial distribution and correlation of PFP and CFP with LVA were assessed. The predictors for CFP were determined.ResultsPFPs displayed low voltages both during AF (median 0.30 mV (Q1-Q3: 0.20-0.50 mV) and SR (median 0.35 mV (Q1-Q3: 0.20-0.56 mV). The duration of PFP-SR was measured at 61 ms (Q1-Q3: 51-76 ms). During SR, most PFP-SRs (89.4 and 97.2%) were located within LVA (<0.5 mV and <1.0 mV, respectively). Areas presenting PFP occurred more frequently in AF than in SR (median: 9.5 vs. 8.0, p = 0.005). Both PFP-AF and PFP-SR were predominantly located at anterior LA (>40%), followed by posterior LA (>20%) and septal LA (>15%). The extent of LVA < 0.5 mV was more extensive in AF (median: 25.2% of LA surface, Q1-Q3:16.6-50.5%) than in SR (median: 12.3%, Q1-Q3: 4.7-29.4%, p = 0.001). CFP in both rhythms occurred in 80% of PFP-SR and 59% of PFP-AF (p = 0.008). Notably, CFP was positively correlated to the extent of LVA in SR (p = 0.004), but not with LVA in AF (p = 0.226). Additionally, the extent of LVA < 0.5 mV in SR was the only significant predictor for CFP, with an optimal threshold of 16% predicting high (>80%) fractionation concordance in AF and SR.ConclusionSubstrate mapping in SR vs. AF reveals smaller areas of low voltage and fewer sites with PFP. PFP-SR are located within low-voltage areas in SR. There is a high degree of spatial agreement (80%) between PFP-AF and PFP-SR in patients with moderate LVA in SR (>16% of LA surface). These findings should be considered when substrate-based ablation strategies are applied in patients with the left atrial low-voltage substrate with recurrent persistent AF.

Dataset Information

Association between serum inflammatory biomarkers and atrial low voltage in patients with atrial fibrillation: A phase 1 FIB-MARK study.

Background

Methods and results

Conclusions

Publications

Association between serum inflammatory biomarkers and atrial low voltage in patients with atrial fibrillation: A phase 1 FIB-MARK study.

Similar Datasets

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