Metabolomic profiling is a new field of research and allows the characterization of new pathways for the discovery of prognostic markers or therapeutic targets. Presently, no    reliable data exist in relation to low-gradient and paradoxical low-flow low-gradient aortic stenosis (LGAS, PLFLGAS).

Objective
We evaluated metabolic changes in patients with LGAS and PLFLGAS before and after transcatheter aortic valve implantation (TAVI) and assessed whether the procedure is capable to reverse metabolic alterations.

188 serum metabolites (AbsoluteIDQ kit p180, Biocrates) were quantified by liquid chromatography tandem mass spectrometry in 21 patients with classical LGAS as well as in 19 patients with PLFLGAS at two different time-points (pre-TAVI and 6 weeks post-TAVI). 20 patients without cardiovascular diseases served as healthy controls (HC). Significantly altered metabolites (using Bonferroni correction) were then correlated to an extensive patient database of clinical parameters at the time-point of the measurement. 

Of all the measured metabolits, 126 (67%) and 122 (64.9%) were significantly altered in LGAS and PLFLGAS patients pre-TAVI, respectively, compared to HC. In detail, acylcarnitines (AC) as well as biogenic amines (BA) were mainly increased in LGAS, whereas phosphatidylcholines (PC) and sphingomyelins (SM) showed significant reductions. In PLFLGAS, again we found AC and BA increased and PC and SM mainly reduced. In LGAS patients post-TAVI, 15 (8%) of metabolites showed significant differences when compared to LGAS pre-TAVI. In PLFLGAS, 23 (12.2%) metabolites showed significant alterations comparing pre- and post-TAVI. Moreover, in LGAS we found 9 and in PLFLGAS 17 metabolites showing reversible concentration levels 6 weeks after TAVI (see Fig.). Correlation analysis between metabolite levels and clinically parameters revealed strong correlations between AC and BNP (r=0.704), AC and CRP (r=0.827), PC and creatinine (r=0.722), and strong inverse correlation between SM and LVEF (r=-0.545) (p<0.01).

Metabolic profiling revealed significant differences in both, LGAS and PLFLGAS, when compared to HC and showed partial reversibility in both patient groups post-TAVI. The correlation of circulating metabolites with clinical parameters might identify novel biomarkers for disease characterization with distinct diagnostic and therapeutic potential.

 

Heatmap of selected metabolites showing the group averages of (a) 9 reversible metabolites in serum levels of LGAS patients and (b) 17 reversible metabolites in PLFLGAS patients. (red boxes) metabolites present in both groups.