Dataset Information

Prognostic implications of valvular heart disease in patients with non-valvular atrial fibrillation.

ABSTRACT:

Background

Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF.

Methods

This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction.

Results

In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17-2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09-2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35-4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization.

Conclusion

Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis.

SUBMITTER: Samaras A

PROVIDER: S-EPMC8449469 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Among the potential factors which may contribute to the development and perpetuation of atrial fibrillation, dysregulation of miRNAs has been suggested. Thus in this study, we have quantified the basal expressions of 662 mature human miRNAs in left atrium (LA) from patients undergoing cardiac surgery for valve repair, suffering or not from atrial fibrillation (AF) by using TaqMan® Low Density arrays (v2.0).Among the 299 miRNAs expressed in all patients, 42 miRNAs had altered basal expressions in patients with AF. Binding-site predictions with Targetscan (conserved sites among species) indicated that the up- and down-regulated miRNAs controlled respectively 3,310 and 5,868 genes. To identify the most relevant cellular functions under the control of the altered miRNAs, we focused on the 100 most targeted genes of each list and identified 5 functional protein-protein networks among these genes. Up-regulated networks were involved in synchronisation of circadian rythmicity and in the control of the AKT/PKC signaling pathway (i.e., proliferation/adhesion). Down-regulated networks were the IGF-1 pathway and TGF-beta signaling pathway and a network involved in RNA-mediated gene silencing, suggesting for the first time that alteration of miRNAs in AF would also perturbate the whole miRNA machinery. Then we crossed the list of miRNA predicted genes, and the list of mRNAs altered in similar patients suffering from AF and we found that respectively 44.5% and 55% of the up- and down-regulated mRNA are predicted to be conserved targets of the altered miRNAs (at least one binding site in 3'-UTR). As they were involved in the same biological processes mentioned above, these data demonstrated that a great part of the transcriptional defects previously published in LA from AF patients are likely due to defects at the post-transcriptional level and involved the miRNAs.Our stringent analysis permitted us to identify highly targeted protein-protein networks under the control of miRNAs in LA and, among them, to highlight those specifically affected in AF patients with altered miRNA signature. Further studies are now required to determine whether alterations of miRNA levels in AF pathology are causal or represent an adaptation to prevent cardiac electrical and structural remodeling.