Pre-operative serum levels of reelin showed diagnostic potential for predicting post-operative atrial fibrillation in aortic stenosis patients (AUC 0.697, p=0.000).
Observational (n=382)
Do preoperative serum markers predict post-operative atrial fibrillation in patients with severe aortic stenosis undergoing surgical valve replacement?
Preoperative serum markers, particularly reelin, show potential in predicting post-operative atrial fibrillation in patients undergoing surgical valve replacement for severe aortic stenosis.
Effect estimate: AUC 0.697
p-value: p=0.000
Abstract Background Post-operative atrial fibrillation (POAF) is the commonest complication after cardiac surgery accounting for 40% of surgical valve replacements, consistently impacting morbimortality rates and financial liability. The heterogeneity of POAF cohorts (e.g., coronary and valvular patients) analyzed in previous biomarker studies limits drawing conclusions with clinical applications. Purpose We sought to identify whether serum markers may infer the underlying pathogenesis driving POAF and predict its occurrence in patients with aortic stenosis (AS) undergoing surgical valve replacement. Methods Pre-operative serums were collected from 382 patients undergoing elective surgical valve replacement for severe AS (80.76% sinus rhythm). POAF was reported in 22.44% patients. Proteomic discovery studies were conducted applying Proximity Extension™ Assay technology in n=41 patients (39.02% POAF). Subsequent functional annotation enrichment analyses were performed and selected targets were validated. Systemic markers of inflammation, endothelial dysfunction, angiogenesis, clinical and demographic parameters were assessed. Results Multivariate analyses of the target-directed proteomics revealed 11 targets significantly or tendentiously regulated in AS patients developing POAF. Enrichment analysis suggested that neutrophil degranulation (MPO, AZU1, PRTN3, CSTB, MMP-9) might be instrumental to POAF in AS. The neutrophil degranulation marker MPO (p=0.011) was further validated in the whole cohort along with relevant markers for inflammation, endothelial dysfunction and angiogenesis. Moreover, MPO was significantly correlated with additional neutrophil degranulation markers (AZU1, PRTN3, MMP-9, NGAL), with the expression of vWF and sVEGF-R2 (endothelial dysfunction) as well as with reelin and VEGF-D (lymphangiogenesis) that may support the development of atrial substrate and ulterior POAF. ROC analyses suggest a diagnostic potential for reelin (AUC 0.697, p=0.000, 76.7% precision) and VEGF-R2 (AUC=0.624, p=0.014, 37.7% precision) in AS patients. Additional logistic regression modelling including MPO, VEGFR2, VEGF-D and Reelin revealed that the latter was the best marker to forecast POAF occurrence (p=0.044), overall, in women (p=0.012). Conclusions Pre-operational analysis of serum markers may infer the underlying pathogenesis driving POAF and assist on everyday decision-making strategies aiming at improving the long-term outcome of AS patients undergoing surgical valve replacement.
Jover et al. (Fri,) conducted a observational in Severe aortic stenosis (n=382). Pre-operative serum markers (Reelin, VEGF-R2, MPO) was evaluated on Post-operative atrial fibrillation (POAF) (AUC 0.697, p=0.000). Pre-operative serum levels of reelin showed diagnostic potential for predicting post-operative atrial fibrillation in aortic stenosis patients (AUC 0.697, p=0.000).