Division of Cardiology, Angiology, Pneumology and Intensive Medical Care, Department of Internal Medicine I, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany.
Department of Clinical Chemistry and Laboratory Diagnostics, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany.
Clin Res Cardiol. 2021 Mar;110(3):399-410. doi: 10.1007/s00392-020-01754-2. Epub 2020 Oct 14.
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.
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.
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).
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.
本研究旨在评估经导管主动脉瓣置换术（TAVR）前后主动脉瓣狭窄（AS）患者的代谢变化，并评估该手术是否逆转代谢组学改变。
通过液相色谱串联质谱法对 30 例严重高梯度主动脉瓣狭窄患者（TAVR 前和 TAVR 后 6 周）和 20 例健康对照者（HC）的 188 种血浆代谢物进行定量分析。然后将显著改变的代谢物与测量时的大量患者临床参数数据库相关联。
在所确定的代谢物中，有 26.6%（n=50）在 TAVR 前的 AS 患者中与 HC 相比发生显著改变。具体而言，5/40 酰基辅酶 A 和 10/42 氨基酸和生物胺在 AS 中主要增加，而 29/90 甘油磷脂和 6/15 鞘磷脂主要减少。在 TAVR 后组中，与 TAVR 前相比，有 10.1%（n=19）的代谢物显示出显著差异。此外，我们发现有 9 种代谢物的浓度水平具有可逆转性。与临床重要参数的相关性研究表明，鞘磷脂与胆固醇之间存在强相关性（r=0.847），酰基辅酶 A 与脑钠肽之间存在强相关性（r=0.664），并且酰基辅酶 A 与左心室射血分数改善呈负相关（r=-0.513），而磷脂酰胆碱与左心室质量改善呈负相关（r=-0.637）。
代谢组学分析鉴定出 AS 患者循环代谢物存在显著且可逆转的变化。循环代谢物与临床参数的相关性支持将这些数据用于识别疾病筛查、病理生理研究以及患者监测的新的诊断和预后标志物。
