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Title: Markers of left atrial fibrosis in atrial fibrillation and prediction of successful rhythm control intervention
Author: Begg, Gordon Andrew
ISNI:       0000 0004 8510 2785
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2019
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Introduction Methods to restore atrial fibrillation (AF) to sinus rhythm include catheter ablation and electrical cardioversion. Myocardial fibrosis is associated with recurrence and may be measurable using circulating biomarkers. Other methods include cardiac magnetic resonance (CMR) and electro-anatomical mapping. The aims were: 1) Compare biomarkers in AF patients and controls. 2) Assess biomarker levels at multiple sampling sites. 3) Determine associations between methods of fibrosis quantification. 4) Determine their predictive value for arrhythmia recurrence. Methods 93 AF ablation patients, 79 cardioversion patients, and 40 control patients were enrolled. Enzyme-linked immunosorbent assay was used to determine peripheral serum levels of galectin-3 (gal-3), type I collagen C terminal peptide (ICTP), type III procollagen N terminal peptide (PIIINP), and fibroblast growth factor 23 (FGF-23). Additionally, in ablation patients, levels were measured in the coronary sinus and both atria. 31 ablation patients underwent CMR. Follow up was 12 months. Results ICTP levels were higher in ablation patients than in controls (p=0.007). Peripheral ICTP levels were higher than intracardiac levels (p < 0.001), and CS levels were higher than atrial levels (p < 0.001). Peripheral gal-3 levels were higher than left atrial levels (p=0.001). FGF-23 was weakly predictive of AF recurrence after cardioversion (HR 1.003 p=0.012). No other biomarkers predicted AF recurrence. Low voltage in the left atrium was the only independent predictor of AF recurrence, mapped in sinus rhythm (HR 4.323 p=0.014) or AF (HR 5.195 p=0.046). LV extracellular volume was associated with LA pressure (beta 0.49, P=0.008) and coronary sinus ICTP (beta 0.75, P < 0.001). Conclusion There is no clinically useful predictive effect of the biomarkers in this study. Further research into FGF-23 is warranted. Associations between LV extracellular volume, ICTP and LA pressure may suggest elevated ventricular myocardial turnover of type I collagen in this cohort, and a possible link with atrial pathology.
Supervisor: Sven, Plein ; Arun, Holden ; Muzahir, Tayebjee Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available