Abstract Body (Do not enter title and authors here): Background
Various temporary mechanical circulatory support device (t-MCS) options are available for supporting patients in cardiogenic shock. While each device has a different physiological impact on the heart, limited studies compare genetic changes in the heart t-MCS. Here, we compare the impact of a percutaneous left ventricular assist device (pVAD) vs an Intra-aortic balloon pump (IABP) on miRNA expression of the left ventricle in patients being bridged to cardiac replacement.
Hypothesis
Difference in genetic signature exists between patients treated with pVAD vs IABP
Methods
Myocardial tissue was collected at the time of cardiac surgery from 4 patients bridged with a pVAD (Impella 5.5) and 4 bridged with IABP. Samples from each strategy of support were combined. Bulk sequencing was performed on an Illumina Hiseq 4000. Raw data was processed to identify unique sequences with lengths of 18-26 nucleotides and were mapped to miRBase to identify known and novel microRNAs (miRs).
Results
The top upregulated (Fig. 1A) and downregulated (Fig. 1B) miRs had functionality related to endothelial pathology and cell transitions (miR 422,378 &92a, miR-653, miR-144). For example, miR 21 has been shown to represent a pathogenic state in cancer and cardiac disease and was found to be significantly lower in heart failure patients supported with pVAD when compared to patients supported with IABP. Gene set enrichment analysis of all the downregulated miRs was performed using miRNA enrichment analysis and annotation tool (miEAA). UpSet plots (Fig. 1C) of the downregulated miRs exhibited a regulatory role in inflammatory and cancer-based genes. KEGG enrichment analysis of target genes of the differentially expressed miRs exhibited that 1000 genes were associated with metabolic pathways (hsa01100), followed by 500 genes in cancer pathways (hsa05200) (Fig. 1D).
Conclusion
Our results suggest that direct cardiac unloading using a p-VAD might have a better improvement of the pathological milieu of heart failure when compared to counter-pulsation unloading. The choice of t-MCS to support myocardial recovery might be important. Our future work will include a prospective study with temporal evaluation of patient’s blood for miRNA profiling.