Abstract 4142969: Temporary Mechanical Circulatory Support Modulates Inflammation And Fibrosis In Cardiogenic Shock Patients Bridged To Cardiac Replacement.

Background: Temporary mechanical circulatory support devices (t-MCS) facilitate recovery of the patients, to then bridge them to cardiac replacement. A new paradigm of resting and recovering the heart with a t-MCS device is being explored. The understanding of mechanisms of recovery with t-MCS’s could facilitate the modulation of specific pathways to promote recovery. We compare the impact of two widely used t-MCS strategies in heart failure (HF): percutaneous left ventricular assist device (HFpVAD) vs Intra-aortic balloon pump (HFIABP) on the genetic landscape of the heart tissue in patients being bridged to cardiac replacement. Hypothesis Cardiac tissue of patients treated with pVAD will have distinct changes when compared to IABP supported hearts in relation to unsupported heart failure tissue. Methods: Myocardial tissue was collected at the time of surgery from 4 patients bridged with a pVAD (Impella 5.5) and 4 bridged with IABP. Tissues from patients who were bridged without MCS were used as HF tissues. Bulk RNA paired-end sequencing of cardiac tissues was performed on an Illumina Hiseq 4000 was performed. StringTie was used to perform expression levels for mRNAs. Results: Gene ontology (GO) analysis of the differentially expressed genes (DEG) resulted in GO terms such as extracellular matrix, cytokine activity, and adaptive immune response indicated that most of the DEG were contributing to the regulation of fibrosis and inflammation related functions. KEGG analysis of the DEG resulted in pathway terms such as malaria, complement and coagulation cascades, ECM receptor interaction, and cell adhesion molecules. Interestingly, the predominance of ECM/fibrosis-related pathways and infection/immune system pathways in both GO and KEGG analysis signals the involvement of these pathways in the t-MCS assisted resting of the cardiac tissue in patients with cardiogenic shock. Conclusion: Our results illustrate that t-MCS in general modulates fibrosis and inflammation related genes with unloading with p-VAD having distinct changes with more genes when compared to IABP support. Further studies exploring these mechanisms could discover a therapeutic focus for promoting t-MCS assisted myocardial recovery.