Dataset Information

Impact of Midregional N-Terminal Pro-Atrial Natriuretic Peptide and Soluble Suppression of Tumorigenicity 2 Levels on Heart Rhythm in Patients Treated With Catheter Ablation for Atrial Fibrillation: The Biorhythm Study.

ABSTRACT: Background We assessed the impact of preprocedural plasma levels of MRproANP (midregional N-terminal pro-atrial natriuretic peptide) and sST2 (soluble suppression of tumorigenicity 2) on recurrence of atrial fibrillation (AF) at 1 year after catheter ablation of AF. Methods and Results This was a prospective, multicenter, observational study including patients undergoing catheter ablation of AF. MRproANP and sST2 were measured in a peripheral venous blood preprocedure, and MRproANP was assessed in the right and left atrial blood during ablation. The primary end point was recurrent AF between 3 and 12 months postablation, defined as a documented (>30 seconds) episode of AF, flutter, or atrial tachycardia. We included 106 patients from December 2017 to March 2019; 105 had complete follow-up, and the mean age was 63 years with 74.2% males. Overall, 34 patients (32.1%) had recurrent AF. In peripheral venous blood, MRproANP was significantly higher in patients with recurrent AF (median, 192.2; [quartile 1-quartile 3, 155.9-263.9] versus 97.1 [60.9-150.7] pmol/L; P<0.0001), as was sST2 (median, 30.3 [quartile 1-quartile 3, 23.3-39.3] versus 23.4 [95% CI, 17.4-33.0] ng/mL; P=0.0033). In the atria, MRproANP was significantly higher than in peripheral blood and was higher during AF than during sinus rhythm. Receiver operating characteristic curve analysis identified a threshold of MRproANP>107.9 pmol/L to predict AF recurrence at 1 year and a threshold of >26.7 ng/mL for sST2. By multivariate analysis, MRproANP>107.9 pmol/L was the only independent predictor of recurrent AF (OR, 24.27; 95% CI, 4.23-139.18). MRproANP<107.9 pmol/L identified subjects at very low risk of recurrence (negative predictive value >95%). Conclusions Elevated MRproANP level independently predicts recurrent AF, whereas sST2 levels do not appear to have any prognostic value in assessing the risk of recurrence of AF up to 1 year after catheter ablation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03351816.

SUBMITTER: Badoz M

PROVIDER: S-EPMC8403329 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Left atrial enlargement and persistent atrial fibrillation (AF) are well-known predictors for arrhythmia recurrence after AF catheter ablation (LRAF). In this study, by using pathway enrichment analysis of GWAS data, we tested the hypothesis that genetic pathways associated with these phenotypes are also associated with LRAF.Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) undergoing de-novo AF catheter ablation were genotyped for ~1,000,000 SNPs. SNPs found to be significantly associated with left atrial diameter (LAD) or AF type were used for gene-based association tests in a systematic biological Knowledge-based mining system for Genome-wide Genetic studies (KGG). Associated genes were tested for pathway enrichment using WEB-based Gene SeT AnaLysis Toolkit (WebGestalt), the Gene Annotation Tool to Help Explain Relationships (GATHER) and the databases provided by Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second step, the association of consistently enriched pathways and LRAF was tested.By using sequential 7-day Holter ECGs, LRAF between 3 and 12 months was observed in 48% and was associated with LAD (B = 1.801, 95% CI 0.760-2.841, p = 1.0E-3) and persistent AF (OR = 2.1; 95% CI 1.567-2.931, p = 2.0E-6). WebGestalt (adj. p = 2.7E-22) and GATHER (adj. p = 5.2E-3) identified the calcium signaling pathway (hsa04020) as the only consistently enriched pathway for LAD, while the extracellular matrix (ECM) -receptor interaction pathway (hsa04512) was the only consistently enriched pathway for AF type (adj. p = 2.1E-15 in WebGestalt; adj. p = 9.3E-4 in GATHER). Both calcium signaling (adj. p = 2.2E-17 in WebGestalt; adj. p = 2.9E-2 in GATHER) and ECM-receptor interaction (adj. p = 1.2E-10 in WebGestalt; adj. p = 2.9E-2 in GATHER) were significantly associated with LRAF.Calcium signaling and ECM-receptor interaction pathways are associated with LAD and AF type and, in turn, with LRAF. Future and larger studies are necessary to replicate and apply these findings.

Project description:AF is a heterogeneous rhythm disorder that is related to a wide spectrum of etiologies and has broad clinical presentations. Mechanisms underlying AF are complex and remain incompletely understood despite extensive research. They associate interactions between triggers, substrate and modulators including ionic and anatomic remodeling, genetic predisposition and neuro-humoral contributors. The pulmonary veins play a key role in the pathogenesis of AF and their isolation is associated to high rates of AF freedom in patients with paroxysmal AF. However, ablation of persistent AF remains less effective, mainly limited by the difficulty to identify the sources sustaining AF. Many theories were advanced to explain the perpetuation of this form of AF, ranging from a single localized focal and reentrant source to diffuse bi-atrial multiple wavelets. Translating these mechanisms to the clinical practice remains challenging and limited by the spatio-temporal resolution of the mapping techniques. AF is driven by focal or reentrant activities that are initially clustered in a relatively limited atrial surface then disseminate everywhere in both atria. Evidence for structural remodeling, mainly represented by atrial fibrosis suggests that reentrant activities using anatomical substrate are the key mechanism sustaining AF. These reentries can be endocardial, epicardial, and intramural which makes them less accessible for mapping and for ablation. Subsequently, early interventions before irreversible remodeling are of major importance. Circumferential pulmonary vein isolation remains the cornerstone of the treatment of AF, regardless of the AF form and of the AF duration. No ablation strategy consistently demonstrated superiority to pulmonary vein isolation in preventing long term recurrences of atrial arrhythmias. Further research that allows accurate identification of the mechanisms underlying AF and efficient ablation should improve the results of PsAF ablation.

Dataset Information

Impact of Midregional N-Terminal Pro-Atrial Natriuretic Peptide and Soluble Suppression of Tumorigenicity 2 Levels on Heart Rhythm in Patients Treated With Catheter Ablation for Atrial Fibrillation: The Biorhythm Study.

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