Clinical effectiveness, biological predictors, and cost-implications of ablation in non-paroxysmal atrial fibrillation
File(s)
Author(s)
Boyalla, Vennela
Type
Thesis
Abstract
Atrial fibrillation (AF) is the most prevalent arrhythmia, and its symptoms negatively impact quality of life. Symptom management in non-paroxysmal AF (non-PAF) is challenging. Rate control has proved inadequate, while rhythm control [i.e. anti-arrhythmic drugs (AAD), catheter ablation (CA)] produces poor results. Surgical ablation (SA) was superior in arrhythmic outcomes for AF patients in previous trials. However, results from the CASA-AF study comparing SA and CA in long-standing persistent AF (LSPAF) revealed that both strategies had equal efficacy at rhythm outcomes at 12 months, with CA superior in improving quality of life.
The central hypothesis was that SA is superior to CA in long-term follow-up (36 months) using continuous cardiac monitoring. We recruited patients from the CASA-AF trial who had undergone CA and SA after randomisation. At 36-months, the proportion of patients free from atrial arrhythmia decreased similarly in both arms. The previous superiority of CA over SA based on quality-of-life scores at 12-months did not persist at 36 months. CA was more cost-effective than SA and AADs in the long term in the context of treating non-PAF.
Several protein interactions underlie the pathological atrial substrate formation, and understanding their potential roles may help identify biomarkers predictive of AF ablation outcomes. We conducted a systematic review that showed >75 proteins were identified in AF ablation studies. Meta-analytical methods narrowed them to five (NT-proBNP, BNP, hsCRP, CITP and IL-6) biomarkers strongly associated with ablation outcomes, none have been translated into clinical practice. Large scale study of proteins (proteomics) was applied to identify novel biomarkers from pre-procedural blood tests to predict ablation success in a sub-cohort of these patients. Cell regulation, inflammation and cardiovascular panels were chosen to cover an extensive range of biological pathways. This work demonstrated that increased markers of inflammation (CD8A + MCP1 + CD40) were jointly predictive of ablation failure in LSPAF.
The central hypothesis was that SA is superior to CA in long-term follow-up (36 months) using continuous cardiac monitoring. We recruited patients from the CASA-AF trial who had undergone CA and SA after randomisation. At 36-months, the proportion of patients free from atrial arrhythmia decreased similarly in both arms. The previous superiority of CA over SA based on quality-of-life scores at 12-months did not persist at 36 months. CA was more cost-effective than SA and AADs in the long term in the context of treating non-PAF.
Several protein interactions underlie the pathological atrial substrate formation, and understanding their potential roles may help identify biomarkers predictive of AF ablation outcomes. We conducted a systematic review that showed >75 proteins were identified in AF ablation studies. Meta-analytical methods narrowed them to five (NT-proBNP, BNP, hsCRP, CITP and IL-6) biomarkers strongly associated with ablation outcomes, none have been translated into clinical practice. Large scale study of proteins (proteomics) was applied to identify novel biomarkers from pre-procedural blood tests to predict ablation success in a sub-cohort of these patients. Cell regulation, inflammation and cardiovascular panels were chosen to cover an extensive range of biological pathways. This work demonstrated that increased markers of inflammation (CD8A + MCP1 + CD40) were jointly predictive of ablation failure in LSPAF.
Version
Open Access
Date Issued
2022-10-07
Date Awarded
2024-02-01
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Wong, Tom
Harding, Sian
Sponsor
National Institute for Health Research (Great Britain)
Grant Number
NIHR200595
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)