☆ 4.5 Article

Metabolomic profiling of patients with high gradient aortic stenosis undergoing transcatheter aortic valve replacement

CLINICAL RESEARCH IN CARDIOLOGY (2021)

Journal

CLINICAL RESEARCH IN CARDIOLOGY

Volume 110, Issue 3, Pages 399-410

Publisher

SPRINGER HEIDELBERG

DOI: 10.1007/s00392-020-01754-2

Keywords

Metabolomics; Aortic stenosis; Transcatheter valve replacement; Prognostic marker

Funding

Projekt DEAL

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Abstract

The study found significant and reversible changes in circulating metabolites of patients with AS. Some metabolites showed strong correlations with clinical parameters, supporting the use of these data to identify novel diagnostic and prognostic markers for disease screening, pathophysiological studies, and patient surveillance.

Aim Aim of our study was to evaluate metabolic changes in patients with aortic stenosis (AS) before and after transcatheter aortic valve replacement (TAVR) and to assess whether this procedure reverses metabolomic alterations. Methods 188 plasma metabolites of 30 patients with severe high-gradient aortic valve stenosis (pre-TAVR and 6 weeks post-TAVR) as well as 20 healthy controls (HC) were quantified by liquid chromatography tandem mass spectrometry. Significantly altered metabolites were then correlated to an extensive patient database of clinical parameters at the time of measurement. Results Out of the determined metabolites, 26.6% (n = 50) were significantly altered in patients with AS pre-TAVR compared to HC. In detail, 5/40 acylcarnitines as well as 10/42 amino acids and biogenic amines were mainly increased in AS, whereas 29/90 glycerophospholipids and 6/15 sphingomyelins were mainly reduced. In the post-TAVR group, 10.1% (n = 19) of metabolites showed significant differences when compared to pre-TAVR. Moreover, we found nine metabolites revealing reversible concentration levels. Correlation with clinically important parameters revealed strong correlations between sphingomyelins and cholesterol (r = 0.847), acylcarnitines and brain natriuretic peptide (r = 0.664) and showed correlation of acylcarnitine with an improvement of left ventricular (LV) ejection fraction (r = - 0.513) and phosphatidylcholines with an improvement of LV mass (r = - 0.637). Conclusion Metabolic profiling identified significant and reversible changes in circulating metabolites of patients with AS. The correlation of circulating metabolites with clinical parameters supports the use of these data to identify novel diagnostic as well as prognostic markers for disease screening, pathophysiological studies as well as patient surveillance.

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Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement

Andreas Mangold, Anna S. Ondracek, Thomas M. Hofbauer, Tyler Artner, Johanna Nechvile, Noel G. Panagiotides, Moritz Mirna, Matthias Hammerer, Dzeneta Fejzic, Uta Hoppe, Bernhard Wernly, Alexander Lauten, Brunilda Alushi, Marcus Franz, Paul C. Schulze, Evelyne Wohlschlaeger-Krenn, Irene M. Lang, Michael Lichtenauer

Summary: This study investigated the levels of double-stranded DNA and deoxyribonuclease activity in plasma after TAVR, finding that baseline double-stranded DNA was significantly higher compared to healthy controls, peaked at 3 and 7 days post-TAVR, and then declined. Additionally, decreased deoxyribonuclease activity at baseline was associated with higher C-reactive protein levels and mean transaortic gradient after 12 months, serving as a strong independent predictor of outcome post-TAVR.

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION (2021)