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American Heart Association

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Final ID: 4139918

Myocardial Transcriptomics Differentiates Decompensated, Compensated, and Healthy Right Ventricular Samples in End Stage Heart Failure

Abstract Body (Do not enter title and authors here):
Introduction:
Myocardial transcriptional changes in the right ventricle (RV) during stress and failure are poorly understood. We hypothesized that myocardial transcriptomic signatures would differ among decompensated (d-RV), compensated (c-RV), and healthy RV (h-RV) myocardium.

Methods:
We obtained RV free-wall myocardial samples from pts undergoing transplant for end-stage HF (n=33). Control samples were obtained from unused donor hearts. We defined d-RV by pulmonary arterial pulsatility index
Results:
Controls (n=8) were 44 years [IQR 39-57] and 50% male. HF pts were 53 years [44-61], 63% male, 13 ischemic and 22 non-ischemic, with median LVEF 21% (IQR 16-28%). Principal component analysis demonstrated distinct expression for h-RV vs c-RV and d-RV, but poorly differentiated between c-RV and d-RV (Figure 1A). Volcano plots for pairwise comparisons with differentially expressed genes (DEGs) are displayed in Figure 1B-D. Notable upregulated genes in d-RV and c-RV vs h-RV included NPPA, NPPB, and MYH6. Of the 4171 DEGs of d-RV vs h-RV, 3625 were also identified comparing c-RV vs h-RV. There were 39 DEGs differentiating d-RV vs c-RV. GSEA identified increased transcription of immune pathways, metabolism, and protein synthesis related pathways in c-RV and d-RV vs h-RV (Figure 2A). c-RV vs d-RV featured increased protein synthesis and decreased immune system and catabolism related pathways (Figure 2B).

Conclusions:
The RV response to stress in end-stage HF features transcriptional increases in immune pathways and protein synthesis along with metabolic changes in fatty acid synthesis, insulin signaling, and steroid biosynthesis. These findings warrant further mechanistic investigation of the implicated pathways.
  • Garry, Jonah  ( Vanderbilt University Medical Center , Nashville , Tennessee , United States )
  • Davogustto, Giovanni  ( Vanderbilt University Medical Center , Nashville , Tennessee , United States )
  • Agrawal, Vineet  ( Vanderbilt University Medical Center , Nashville , Tennessee , United States )
  • Brittain, Evan  ( Vanderbilt University Medical Center , Nashville , Tennessee , United States )
  • Author Disclosures:
    Jonah Garry: DO NOT have relevant financial relationships | Giovanni Davogustto: No Answer | Vineet Agrawal: No Answer | Evan Brittain: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Thomas Smith Memorial Lecture

Monday, 11/18/2024 , 09:45AM - 11:00AM

Abstract Oral Session

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