Interventional Left Atrial Appendage Closure Affects the Metabolism of Acylcarnitines

Christian Fastner, Michael Behnes, Benjamin Sartorius, Annika Wenke, Siegfried Lang, Gökhan Yücel, Katherine Sattler, Jonas Rusnak, Ahmad Saleh, Christian Barth, Kambis Mashayekhi, Ursula Hoffmann, Martin Borggrefe, Ibrahim Akin, Christian Fastner, Michael Behnes, Benjamin Sartorius, Annika Wenke, Siegfried Lang, Gökhan Yücel, Katherine Sattler, Jonas Rusnak, Ahmad Saleh, Christian Barth, Kambis Mashayekhi, Ursula Hoffmann, Martin Borggrefe, Ibrahim Akin

Abstract

Background: Left atrial appendage closure (LAAC) represents the interventional alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). The metabolism of acylcarnitines was shown to affect cardiovascular diseases. This study evaluates the influence of successful LAAC on the metabolism of acylcarnitines.

Methods: Patients undergoing successful LAAC were enrolled prospectively. Peripheral blood samples for metabolomics measurements were collected immediately before (i.e., index) and six months after LAAC (i.e., mid-term). A targeted metabolomics analysis based on electrospray ionization-liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed.

Results: 44 patients with non-valvular AF (median CHA₂DS₂-VASc score 4, median HAS-BLED score 4) and successful LAAC were included. Significant changes in acylcarnitine levels were found in the total cohort, which were mainly attributed to patients with impaired left ventricular and renal function, elevated amino-terminal pro-brain natriuretic peptide (NT-proBNP) and diabetes mellitus. Adjusted multivariable regression models revealed significant changes of five metabolites over mid-term follow-up: C2, C14:1, C16, and C18:1 decreased significantly (each p < 0.05); short-chain C5 acylcarnitine plasma levels increased significantly (p < 0.05).

Conclusion: This study demonstrates that successful LAAC affects the metabolism of acylcarnitines at mid-term follow-up.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT02985463.

Keywords: acylcarnitines; atrial fibrillation; left atrial appendage; left atrial appendage closure; metabolomics.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hierarchical cluster analysis giving an overview of differences in metabolites between T1 and T2.
Figure 2
Figure 2
Changes of acylcarnitines before and after left atrial appendage closure over mid-term follow-up. (Left) Mean logarithmic changes of carnitine and acylcarnitine plasma levels for each analyzed metabolite; (right) percentage change.
Figure 3
Figure 3
Metabolomic pathway of acylcarnitine utilization and influence of the left atrial appendage closure over the mid-term follow-up. ** indicate statistical significance after regression analysis (p < 0.05), * indicates a statistical trend (p < 0.1); AC = acylcarnitine, CoA = co-enzyme A, TCA = tricarboxylic acid.

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