Single-Cell Sequencing of PBMC Reveals Monocyte-Mediated Inflammation Is Enhanced in Crizotinib-Induced Paroxysmal Atrial Fibrillation

The cause of atrial fibrillation (AF) is unclear and is associated with organic heart disease, pre-excitation syndrome, and other underlying conditions. Medications may also cause AF, such as chemotherapeutic agents. Crizotinib is used as a multi-target protein kinase inhibitor in the treat-ment of non-small cell lung cancer. The most common adverse events with crizotinib are nausea, diarrhoea and vomiting. There are also side effects such as hepatotoxicity, interstitial pneumonitis, prolonged QT interval, and bradycardia. Here, we report a case of crizotinib-induced AF. For the first time, we used peripheral blood mononuclear cells before and after the onset of paroxysmal AF for single-cell sequencing analysis with the aim of determining the mechanism of AF. The single-cell sequencing results and retrospective study showed that monocytes were the most dynamic cell type in the peripheral blood at the onset of AF and increasing proportion of monocytes is an important feature of atrial fibrillation. Meanwhile, retrospective studies have also shown that a higher level of inflammation is a characteristic of patients with AF. Monocyte-mediated adipogenesis-related sig-naling pathway, GALECTIN signaling, and chemokine overexpression were characteristic of pe-ripheral blood mononuclear cells at the onset of AF. At the same time, we found an elevated level of inflammation and an elevated red cell distribution width (RDW) in this patient. These clinical findings corroborate each other with the results of the single-cell analysis, suggesting that inflam-mation is a very important feature in the development of AF. Overall design: single-cell RNA-seq analysis of the PBMCs from patient in the stage of use (day8), and stage of withdrawal (day16) after crizotinib administration (day0), the patient discontinued crizotinib on day 11, and AF disappeared on day 12.