Atrial Structure and Function and its Implications for Current and Emerging Treatments for Atrial Fibrillation
Section snippets
LA remodelling
The LA is a complex entity displaying a considerable degree of physiological, electrical and anatomical plasticity in disease states.
“Remodelling” refers to electrical and structural alterations to the atrial tissue leading to impairment of normal atrial function. Many disease processes lead to atrial remodelling, including hypertension (HTN), valvular heart disease (VHD) and cardiomyopathy, however, remodelling in the setting of AF is of particular interest as its occurrence appears to
Mechanisms of electrical remodelling
The mechanisms of electrical remodelling in AF are multifaceted. Electrical remodelling facilitates all three arrhythmia mechanisms: enhanced automaticity, triggered activity and re-entry.3 Enhanced automaticity and triggered activity promote spontaneous rapid depolarisations of atrial myocytes. Re-entry is facilitated by processes which shorten atrial effective refractory period (ERP), reduce action potential duration (APD) and slow conduction velocity.4 These changes increase the period of
Anatomical considerations and implications for AF treatments
Before exploring the crucial role of structural remodelling it is worth appreciating the structural aspects of the LA, and its implications on AF development and treatment. The advent of CA for AF, which by its very nature requires an intimate navigation around the LA endocardium, has significantly advanced our anatomical and electrophysiological understanding of LA structure and function. Nonetheless, despite this detailed biological characterisation of the LA, significant debate still exists
Structural remodelling (Fig 3)
Structural remodelling refers to alterations in the tissue architecture of the LA at both a cellular and macroscopic level the hallmark of which is atrial fibrosis, however inflammation and LA mechanical factors also play a role.
Conclusion
Atrial structure and function have direct implications for the management of AF. Electrical remodelling results in a multitude of complex physiological changes, which create conditions favourable to AF development and sustainment. The identification of key molecular pathways improves our understanding of AF mechanisms, and may also provide opportunities for the development of novel pharmacological therapies, of which more are sorely needed. Intrinsic anatomical aspects of the LA have an
Statement of Conflict of Interest
The authors have no conflicts of interest to disclose.
Acknowledgments
Drs Sandeep Prabhu, Alex JA McLellan and Tomos E Walters receive funding from Australian National Health and Medical Research Council (NHMRC) and National Heart Foundation of Australia. Drs Sandeep Prabhu and Alex JA McLellan also receive funding from the Baker IDI Heart and Diabetes Research Institute. Professor M Kistler is supported by practitioner fellowships from the NHMRC. Drs Meenal Sharma and Alex Voskoboinik have no disclosures. This research is supported in part by the Victorian
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