Metabolomic Profiling as a Potential Tool for Predicting Cancer Therapy-Related Cardiovascular Toxicity: a Pilot Single-Center Study

Aim     To determine the array of metabolomic profiles and structural and functional parameters of the vascular wall associated with the risk of cardiovascular toxicity of antitumor therapy (ATT) in oncohematological patients.

Material and methods            This study included 59 patients, among them 34 patients with lymphomas (non-Hodgkin and Hodgkin lymphoma) and 25 with multiple myeloma. Before and after 3 courses of ATT (anthracyclines, proteasome inhibitors), finger photoplethysmography and transthoracic echocardiography were performed as well as metabolomic profiling (98 metabolites) by high-performance liquid chromatography in combination with tandem mass spectrometry. Statistical analysis of the results included parametric and nonparametric tests, logistic regression, and cross-validation.

Results            The study showed that even before the initiation of ATT, cancer patients had signs of endothelial dysfunction and increased vascular wall stiffness (increased aSI, RI, and IO indices), which significantly worsened after the specific treatment. Metabolomic profiling identified a set of metabolites associated with the risk of cardiovascular toxicity, including increased concentrations of amino acids (asparagine, serine, glutamate, glutamine, taurine, citrulline), short-chain acylcarnitines (C18:1 OH-carnitine, C16:1 OH-carnitine, C14OH-carnitine, C2 carnitine), choline metabolism intermediates (TMAO, dimethylglycine, choline), tryptophan metabolites (hydroxyindoleacetic acid, kynurenic acid). Additionally, a logistic regression model was developed based on the analysis of the metabolomic profile, which showed a high prognostic power (AUC = 0.84) for predicting cardiovascular toxicity of ATT.

Conclusion      The study identified key metabolites and structural and functional parameters of blood vessels that allow detection of an increased risk of cardiovascular complications of ATT in patients with lymphomas and multiple myeloma before the initiation of a specific treatment. Increased concentrations of amino acids, acylcarnitines, and choline metabolites may serve as an additional risk factor for the onset/progression of cardiovascular complications. The proposed integrative approach, including both metabolomic profiling and non-invasive assessment of the vascular wall condition, opens broad prospects for personalized cardioprotection of cancer patients and more accurate monitoring of the cardiovascular status during ATT.

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