Consolo Filippo, Barberini Luigi, Fattuoni Claudia, Grapov Dmitry, Montisci Andrea, Pappalardo Federico
Università Vita Salute San Raffaele, Milano, Italy.
Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy.
Ann Cardiothorac Surg. 2021 Mar;10(2):240-247. doi: 10.21037/acs-2020-cfmcs-117.
Metabolomic profiling has important diagnostic and prognostic value in heart failure (HF). We investigated whether left ventricular assist device (LVAD) support has an impact on the metabolomic profile of chronic HF patients and if specific metabolic patterns are associated with the development of adverse events.
We applied untargeted metabolomics to detect and analyze molecules such as amino acids, sugars, fatty acids and other metabolites in plasma samples collected from thirty-three patients implanted with a continuous-flow LVAD. Data were analyzed at baseline, i.e., before implantation of the LVAD, and at long-term follow-up.
Our results reveal significant changes in the metabolomic profile after LVAD implant compared to baseline. In detail, we observed a pre-implant reduction in amino acid metabolism (aminoacyl-tRNA biosynthesis) and increased galactose metabolism, which reversed over the course of support [median follow-up 187 days (63-334 days)]. These changes were associated with improved patient functional capacity driven by LVAD therapy, according to NYHA functional classification of HF (NYHA class I-II: pre-implant =0% of the patients; post-implant =97% of the patients; P<0.001). Moreover, patients who developed adverse thromboembolic events (n=4, 13%) showed a pre-operative metabolomic fingerprint mainly associated with alterations of fatty acid biosynthesis and mitochondrial beta-oxidation of short-chain saturated fatty acids.
Our data provide preliminary evidence that LVAD therapy is associated with changes in the metabolomic profile of HF and suggest the potential use of metabolomics as a new tool to stratify LVAD patients in regard to the risk of adverse events.
代谢组学分析在心力衰竭(HF)中具有重要的诊断和预后价值。我们研究了左心室辅助装置(LVAD)支持是否会对慢性HF患者的代谢组学特征产生影响,以及特定的代谢模式是否与不良事件的发生相关。
我们应用非靶向代谢组学技术,对从33例植入连续血流LVAD的患者采集的血浆样本中的氨基酸、糖类、脂肪酸和其他代谢物等分子进行检测和分析。在基线时(即LVAD植入前)和长期随访时对数据进行分析。
我们的结果显示,与基线相比,LVAD植入后代谢组学特征有显著变化。具体而言,我们观察到植入前氨基酸代谢(氨酰-tRNA生物合成)减少,半乳糖代谢增加,而在支持过程中这些情况发生了逆转[中位随访187天(63 - 334天)]。根据HF的纽约心脏协会(NYHA)功能分级,这些变化与LVAD治疗驱动的患者功能能力改善相关(NYHA I-II级:植入前 = 0%的患者;植入后 = 97%的患者;P<0.001)。此外,发生不良血栓栓塞事件的患者(n = 4,13%)术前的代谢组学指纹主要与脂肪酸生物合成改变和短链饱和脂肪酸的线粒体β-氧化有关。
我们的数据提供了初步证据,表明LVAD治疗与HF患者代谢组学特征的变化相关,并提示代谢组学有可能作为一种新工具,用于对LVAD患者不良事件风险进行分层。