Medicine (RMH) - Theses
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ItemMechanisms of atrial fibrillation in humans: contributions from triggers and substrate( 2011)Atrial fibrillation (AF) remains the most common clinical arrhythmia in humans, causing significant morbidity and mortality. Current understanding involves contributions from initiating triggers and remodelled atrial substrate, however the precise nature of these remains elusive. This thesis evaluates the nature of pulmonary vein (PV) triggers and atrial substrate that contribute towards AF mechanism and the potential for reversal of atrial remodelling. Chapters 2 and 3 are introductory chapters examining the relative importance of triggers (focal PV tachycardia) and atrial substrate (flutter following atrial septal defect (ASD) surgery) by studying the incidence of AF after catheter ablation (RFA). These studies demonstrate that although AF does not occur after elimination of PV triggers in patients without atrial substrate (PV tachycardia), it commonly occurs in patients with atrial substrate (ASD surgery). Chapters 4 and 5 examine the electrophysiologic substrate of the PVs. Chapter 4 demonstrates that the PVs of both paroxysmal (PAF) and persistent AF (PeAF) patients possess lower voltage, shorter muscle sleeves, slowed conduction, altered refractoriness and more complex electrograms compared to controls. Some of the substrate remodelling was more marked in PeAF than PAF patients. Chapter 5 demonstrates that ageing is associated with a reduction in PV voltage, conduction slowing and increased signal complexity without changes in refractoriness. Together, these chapters provide insights into the mechanisms responsible for PV arrhythmogenesis and the increasing prevalence of AF with age. Although complex fractionated electrograms (CFE) are commonly targeted as AF substrate, their significance remains controversial. Chapters 6 and 7 evaluate the significance of CFE in the coronary sinus (CS) and the relationship between CFE seen during AF and paced-rhythm. Chapter 6 demonstrates that both PAF and PeAF patients demonstrate a higher prevalence of CFE and short cycle length activation and slower conduction in the CS than control patients with induced AF. There was no difference in dominant frequency and CFE were also common in the control group. Chapter 7 demonstrates that low-voltage and the proportion of CFE were significantly greater during AF than paced-rhythm. CFE during AF did not correlate with abnormal atrial substrate in paced-rhythm. Together, these chapters highlight that CFE may not always reflect abnormal atrial substrate. Chapter 8 evaluates the left atrial substrate associated with AF and demonstrates that patients with AF have lower voltage, slowed conduction and increased complex signals compared with a control population. Most of these changes were more pronounced in the PeAF than PAF group, providing further insights into the progressive nature of AF. Chapter 9 evaluates the long-term effects of RFA for AF on remodelling of the right atrial substrate. Compared to a control population, there was lower voltage, slowed conduction, increased complex signals, prolonged refractoriness and left atrial dilatation in the AF group at baseline. At 10±13 months following successful ablation, the AF group demonstrated further voltage reduction, no improvement or worsening of conduction and further prolongation of refractoriness despite a reduction in left atrial size. These observations suggest that changes in atrial substrate associated with AF are not reversed by RFA.