The Left Atrial Appendage in Humans: Structure, Physiology, and Pathogenesis

Nabeela Karim; Siew Yen Ho; Edward Nicol; Wei Li; Filip Zemrak; Vias Markides; Vivek Reddy; Tom Wong


Europace. 2020;22(1):5-18. 

In This Article

Non-mechanical Function of the Left Atrial Appendage

The LAA also has an important role to play in volume homeostasis through its non-mechanical properties.

Left Atrial Appendage, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, and Volume Homeostasis

Atrial natriuretic peptide (ANP) is produced in atrial granule cardiocytes, of which the densest concentration exists in the right and left atrial appendages.[34] Brain natriuretic peptide (BNP) is also released from the LAA in addition to the left ventricle in patients with AF.[35] Both peptides act on ANP receptors, thereby exerting the same physiological effects.[36] This includes an increase in renal sodium excretion, reduction in extracellular volume, vasodilation and reduction in blood pressure.[36] Atrial natriuretic peptide release is triggered by stretch receptors, with LAA wall distention being more predictive of ANP release than left atrial distention or left atrial pressure.[37]

Animal models have shown suppression of ANP following atrial appendectomy.[38,39] In humans, the effects of bilateral atrial appendectomy after the maze procedure, also results in a reduction in ANP secretion post-operatively, as well as long term.[40] This may have implications post-operatively, due to a reduction in renal response to fluid load during this period.[40]

Left atrial appendage suture ligation with the LARIAT device (which unlike endocardial LAA occlusion devices, causes LAA necrosis[41]) has been investigated in a single-centre prospective study of 66 patients.[42] There was no significant difference in mean ANP and BNP both prior to the procedure and at 3-month follow-up.[42] These results were corroborated in another study, which showed that after 3 months, ANP and BNP levels normalize following both epicardial and endocardial LAA occlusion.[43] This is in contrast to the study involving surgical appendectomy,[40] however, in that study the timing for ANP measurements differed, with samples taken immediately after intervention and then 2 years later in context of response to exercise.[40] The effects of LAA occlusion with a percutaneous endocardial device, whereby the endocardial body remain intact, has also been investigated.[44] An immediate increase in ANP and BNP followed occlusion; likely due to LAA stretching by introduction of the closure device, with a subsequent decrease in ANP and BNP 24 h later.[44]

Left Atrial Appendage and Other Neurohormonal Factors

In a study that investigated 76 patients undergoing LAA exclusion with the LARIAT device, blood pressure was significantly reduced both post-procedure and at 6 months.[45] A reduction in sodium levels immediately post-procedure was also demonstrated, however, this was not maintained at 6 months, thus the mechanism behind the blood pressure change is unclear.[42,43] Neurohormonal factors that could potentially contribute to the LAA effect on haemodynamics were prospectively measured in 77 patients undergoing LAA epicardial or endocardial closure.[43] Epicardial LAA occlusion resulted in significant down-regulation of the adrenergic system and renin–aldosterone system. Coincidentally, they observed a reduction in systemic blood pressure, reduced levels of plasma adrenaline, noradrenaline, aldosterone, and renin both 24 h post-procedure and at 3 months. This effect was not seen with endocardial devices. In addition, epicardial LAA occlusion resulted in increased levels of adiponectin, insulin and free fatty acids, not replicated with endocardial closure,[43] suggesting LAA involvement in both fat and glucose modulation.[43] Potentially, both roles could be mediated by the dense autonomic innervation of the LAA.[43]