Transcriptional Signatures of the Right Ventricle in End-Stage Heart Failure

The molecular mechanisms driving right ventricular (RV) adaptation to stress and failure in end-stage heart failure (HF) are largely unknown. We aimed to characterize myocardial transcriptional changes in the RV caused by left sided HF and comparing RV compensation to failure. Additionally, we compared transcriptomic changes between right and left ventricular (LV) failure. Paired right and left ventricular myocardial tissue samples were obtained from 33 human subjects with end stage HF referred for transplantation and 8 control donors with unused transplant hearts. RV samples from end stage HF subjects were subdivided into compensated (n = 25) and failing (n = 8) categories based on pulmonary artery pulsatility index of < 1.85. All samples underwent bulk tissue RNA-sequencing. We compared gene expression between groups and performed pathway enrichment analysis. Pathways related to fatty acid metabolism and mitochondrial function were negatively enriched, while extracellular structure-related pathways were positively enriched in stressed RVs (compensated and failing) compared to controls. Compensated and failing RVs were differentiated by transcriptional changes in protein production/processing and immune system pathways. PPAR signaling and fatty acid metabolism pathways were consistently enriched in the RV compared to the LV. The RV has a distinct transcriptional signature under stress and in failure. Overlapping molecular mechanisms may underlie RV failure in pulmonary arterial hypertension and HF. Fatty Acid metabolism and associated signaling pathways appear enriched in the RV compared to the LV.