Transcriptome signature of ventricular arrhythmia in dilated cardiomyopathy reveals increased fibrosis and activated TP53

Aims One-third of DCM patients experience ventricular tachycardia (VT), but a clear biological basis for this has not been established. The purpose of this study was to identify transcriptome signatures and enriched pathways in the hearts of dilated cardiomyopathy (DCM) patients with VT. Methods and results We used RNA-sequencing in explanted heart tissue from 49 samples: 19 DCM patients with VT, 16 DCM patients without VT, and 14 non-failing controls. We compared each DCM cohort to the controls and identified the genes that were differentially expressed in DCM patients with VT but not without VT. Differentially expressed genes were evaluated using pathway analysis, and pathways of interest were investigated by qRT-PCR validation, Western blot, and microscopy. There were 590 genes differentially expressed in DCM patients with VT that are not differentially expressed in patients without VT. These genes were enriched for genes in the TGFs1 and TP53 signaling pathways. Increased fibrosis and activated TP53 signaling was demonstrated in heart tissue of DCM patients with VT. Conclusions Our study supports that distinct biological mechanisms distinguish ventricular arrhythmia in DCM patients.