Occlusion of left atrial appendage affects metabolomic profile: focus on glycolysis, tricarboxylic acid and urea metabolism

Abstract

BackgroundLeft atrial appendage (LAA) closure (LAAC) by implantation of an occlusion device is an established cardiac intervention to reduce risk of stroke while avoiding intake of oral anticoagulation medication during atrial fibrillation. Cardiac interventions can alter local or systemic gene and protein expression. Effects of LAAC on systemic metabolism have not been studied yet.ObjectivesWe aimed to study the effects of interventional LAAC on systemic metabolism.MethodsProducts of glycolysis, tricarboxylic acid and urea metabolism were analyzed by ESI-LC-MS/MS and MS/MS using the AbsoluteIDQ™ p180 Kit in plasma of 44 patients undergoing successful interventional LAAC at baseline (T0) and after 6 months (T1).ResultsDuring follow up, plasma concentrations of several parameters of glycolysis and tricarboxylic acid cycle (TCA) and urea metabolism increased (alanine, hexose, proline, sarcosine), while others decreased (aspartate, glycine, SDMA, serine). Multivariate linear regression analysis showed that time after interventional LAAC was an independent predictor for metabolite changes, including the decrease of SDMA (beta −0.19, p < 0.01) and the increase of sarcosine (beta 0.16, p < 0.01).ConclusionsSuccessful interventional LAAC affects different pathways of the metabolome, which are probably related to cardiac remodeling. The underlying mechanisms as well as the long term effects have to be studied in the future.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-017-1255-2) contains supplementary material, which is available to authorized users.

Plasma Dimethylarginine Levels and Carotid Intima–Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke

“…Moreover, there are recent reports which may support a possible pathogenetic link of the markers investigated in our study with AF: e.g., SDMA but not ADMA has been described to be associated with left atrial diameter and P wave duration in ECG [29]. Successful occlusion of the left atrial appendage, moreover, led to a significant reduction of SDMA [30], further supporting a pathogenetic link of this distinct marker with atrial cardiopathy. Alterations of the gene coding for Alanine–glyoxylate aminotransferase 2, which is the only enzyme that is involved in metabolizing both ADMA and SDMA, were recently considered to be associated with AF [31].…”

A 79‐year‐old woman with atrial fibrillation and new onset of heart failure

“…16 In a recent publication, rehospitalizations for heart failure were reported in 17% of the patients after interventional LAA closure; however, the development of heart failure was attributed to pre-existing cardiac disease in this study. 22,23 At present, the clinical relevance of this phenomenon during long-term follow-up is unknown. 18,19 Progressive left atrial enlargement is a well-known phenomenon in permanent nAF and has also been documented after interventional LAA closure.…”

“…Further potentially disastrous consequences in our patient were a right atrial appendage thrombus and bidirectional interatrial shunting through a Apart from haemodynamic and endocrine consequences, LAA closure has been shown to affect glycolysis, tricarboxylic acid, urea, and lipidome metabolism. 22,23 At present, the clinical relevance of this phenomenon during long-term follow-up is unknown.…”

Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

“…Interestingly, successful occlusion of the left atrial appendage led to a significant reduction of SDMA levels, while no changes concerning ADMA were observed [174]. Moreover, a polymorphism in the gene coding for AGXT2 which metabolizes ADMA and SDMA is associated with AF [175].…”