Acute and chronic atrial remodeling in obstructive sleep apnoea : implications for atrial fibrillation.
Year: 2012
Type: dissertation
Study design: Observational Study
Abstract: Atrial fibrillation (AF), the most common sustained arrhythmia, has been well studied; however, its underlying mechanisms and relationships to other disease processes have not been fully explored. Observational data from epidemiological studies have suggested a relationship between obstructive sleep apnoea (OSA) and AF. Recent clinical studies have implicated an adverse outcome to therapy in patients with AF and OSA. Despite several candidate mechanisms advanced, the acute and chronic changes to the atrial myocardium have not been fully characterised. This thesis evaluates symptomatic patients with AF presenting for \nradiofrequency ablation of their arrhythmia. The acute and chronic electrophysiological and electroanatomical atrial substrate is characterised. Finally the effect on clinical outcomes of therapy directed at AF is evaluated with specific reference to the presence of OSA. Chapter 2 demonstrates the differences in the atrial substrate in paroxysmal and persistent AF. This study found persistent AF was associated with a reduction in electrogram voltage and greater signal fragmentation, with these two attributes being negatively associated. Chapter 3 examines patients presenting with symptomatic AF, previously not known to have sleep disordered breathing. OSA was associated with a greater symptomatic burden of AF as well as chronicity of the arrhythmia. In the presence of more severe OSA, there was a greater chance of failure of radiofrequency ablation in maintaining sinus rhythm. Chapter 4 characterises the underlying atrial substrate resulting in AF in patients with moderate to severe untreated OSA. OSA patients had larger atria, greater areas of low voltage and areas of electrical silence, suggesting loss of atrial myocardium. There were also markedly reduced conduction velocities, longer corrected sinus node recovery times and more conduction abnormalities characterised by complex electrograms. These findings provide important insights into the adverse remodeling that may allow AF to develop and persist in these patients, and promote the failure of ablation strategies. Chapter 5 examines nocturnal atrial electrophysiological alterations resulting from acute episodes of respiratory disturbance associated with hypopnoea and obstructive apnoea events the night after undergoing radiofrequency ablation for AF. Dynamic changes in effective refractory period (ERP), conduction times and conduction delay along linear catheters were documented. The changes appeared to be more marked for obstructive apnoeas than hypopnoeas. This study suggests a dynamic, pro-arrhythmic electrical substrate that could potentially lead to nocturnal triggering of AF and its maintenance. Finally, Chapter 6 describes an ex-vivo rabbit model, created to examine the acute effects of hypoxia (moderate and severe) and hypercapnia. Left atrial ERP, conduction time and conduction heterogeneity were studied using a customised microelectrode array. During hypoxia, there was a dose dependent increase in ERP with only partial resolution on restoration of baseline oxygen levels. With hypercapnia, there was a slower rise in ERP that did not appear to recover. Slowing of conduction was most noted in severe hypoxia, with only partial resolution in recovery. In hypercapnia, there was progressive \nslowing of conduction into recovery. Conduction heterogeneity was also increased in the presence of hypoxia and hypercapnia. These findings further suggest complex alterations to the atrial electrophysiology in the presence of hypoxia and hypercapnia, with dynamic changes to in refractory periods, conduction times and heterogeneity. Together, a greater understanding of the acute and chronic effects of OSA on AF, and an appreciation of the failure of ablation strategies in the presence of this breathing disorder is attained. This paves the way for further studies on the mechanisms involved, and on the potential role for continuous positive airway pressure therapy (CPAP) in the management of patients with OSA and AF.
Author: H. Dimitri
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2511636659